The influence of CCN family proteins on ovarian physiology and pathology
El Arbi Abulghasem

A
Abstract
The CCN family of proteins is comprised of six matricellular proteins known to regulate multiple cellular processes such as adhesion, proliferation, differentiation, and apoptosis. CCN proteins are known to function through the binding of integrin receptors and through the regulation of growth factors and cytokines in the context of cardiovascular and skeletal development, injury repair, fibrosis, inflammation and cancer. The expression and roles of several CCNs, particularly CCN1 and CCN2, have been investigated in the ovary as they are effectors of the Hippo signaling pathway, and their role in the development of ovarian fibrosis has been described. Here we review the patterns of expression of CCN1–6 in the ovarian follicle, and the role of CCN2 in follicle development and steroidogenesis, and the expression and potential actions of CCN1–6 in ovarian cancers. We highlight the roles CCNs may play in inflammatory processes, and put forth a case for CCN involvement in the process of ovulation.
Keywords: CCN, CTGF, cytokine, fibrosis, follicle, Hippo signaling pathway, ovarian cancer, ovulation.
References
Abd El Kader T, Kubota S, Nishida T, Hattori T, Aoyama E, Janune D, Hara ES, Ono M, Tabata Y, Kuboki T, Takigawa M (2014) The regenerative effects of CCN2 independent modules on chondrocytes in vitro and osteoarthritis models in vivo. Bone 59, 180-188.
| Crossref | Google Scholar | PubMed |
Bai T, Chen C-C, Lau LF (2010) Matricellular protein CCN1 activates a proinflammatory genetic program in murine macrophages. The Journal of Immunology 184(6), 3223-3232.
| Crossref | Google Scholar | PubMed |
Banaś M, Olszanecka-Glinianowicz M, Zahorska-Markiewicz B (2006) The role of tumor necrosis factor and interleukin-6 in polycystic ovary syndrome. Polski Merkuriusz Lekarski 21(125), 489-491.
| Google Scholar | PubMed |
Barbolina MV, Adley BP, Kelly DL, Shepard J, Fought AJ, Scholtens D, Penzes P, Shea LD, Stack MS (2009) Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. International Journal of Cancer 125(4), 816-825.
| Crossref | Google Scholar |
Batmunkh R, Nishioka Y, Aono Y, Azuma M, Kinoshita K, Kishi J, Makino H, Kishi M, Takezaki A, Sone S (2011) CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin β1/focal adhesion kinase pathway. The Journal of Medical Investigation 58(3-4), 188-196.
| Crossref | Google Scholar | PubMed |
Berkholtz CB, Lai BE, Woodruff TK, Shea LD (2006) Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis. Histochemistry and Cell Biology 126(5), 583-592.
| Crossref | Google Scholar | PubMed |
Berschneider B, Ellwanger DC, Baarsma HA, Thiel C, Shimbori C, White ES, Kolb M, Neth P, Königshoff M (2014) miR-92a regulates TGF-β1-induced WISP1 expression in pulmonary fibrosis. The International Journal of Biochemistry & Cell Biology 53, 432-441.
| Crossref | Google Scholar |
Blaha M, Nemcova L, Kepkova KV, Vodicka P, Prochazka R (2015) Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides. Reproductive Biology and Endocrinology 13, 113.
| Crossref | Google Scholar |
Bork P (1993) The modular architecture of a new family of growth regulators related to connective tissue growth factor. FEBS Letters 327(2), 125-130.
| Crossref | Google Scholar |
Borkham-Kamphorst E, Steffen BT, van de Leur E, Haas U, Weiskirchen R (2018) Portal myofibroblasts are sensitive to CCN-mediated endoplasmic reticulum stress-related apoptosis with potential to attenuate biliary fibrogenesis. Cellular Signalling 51, 72-85.
| Crossref | Google Scholar | PubMed |
Bradham DM, Igarashi A, Potter RL, Grotendorst GR (1991) Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. The Journal of Cell Biology 114(6), 1285-1294.
| Crossref | Google Scholar |
Brown HM, Dunning KR, Robker RL, Pritchard M, Russell DL (2006) Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis. Developmental Biology 300(2), 699-709.
| Crossref | Google Scholar |
Chang H-M, Cheng J-C, Liu Y, Klausen C, Xu C, Leung PCK (2016a) Activin A-induced increase in LOX activity in human granulosa-lutein cells is mediated by CTGF. Reproduction 152(4), 293-301.
| Crossref | Google Scholar |
Chang H-M, Fang Y, Liu P-P, Cheng J-C, Yang X, Leung PCK (2016b) Connective tissue growth factor mediates growth differentiation factor 8-induced increase of lysyl oxidase activity in human granulosa-lutein cells. Molecular and Cellular Endocrinology 434, 186-198.
| Crossref | Google Scholar |
Chang H-M, Pan H-H, Cheng J-C, Zhu Y-M, Leung PCK (2016c) Growth differentiation factor 8 suppresses cell proliferation by up-regulating CTGF expression in human granulosa cells. Molecular and Cellular Endocrinology 422, 9-17.
| Crossref | Google Scholar |
Chang H-M, Bai L, Zhu Y-M, Leung PCK (2022) Connective tissue growth factor mediates bone morphogenetic protein 2-induced increase in hyaluronan production in luteinized human granulosa cells. Reproductive Biology and Endocrinology 20(1), 65.
| Crossref | Google Scholar |
Chen C-C, Lau LF (2009) Functions and mechanisms of action of CCN matricellular proteins. The International Journal of Biochemistry & Cell Biology 41(4), 771-783.
| Crossref | Google Scholar |
Chen C-C, Young JL, Monzon RI, Chen N, Todorović V, Lau LF (2007) Cytotoxicity of TNFα is regulated by integrin-mediated matrix signaling. The EMBO Journal 26(5), 1257-1267.
| Crossref | Google Scholar |
Chen C-Y, Fuh L-J, Huang C-C, Hsu C-J, Su C-M, Liu S-C, Lin Y-M, Tang C-H (2017) Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy. Scientific Reports 7(1), 421.
| Crossref | Google Scholar |
Cheng J-C, Chang H-M, Fang L, Sun Y-P, Leung PCK (2015) TGF-β1 up-regulates connective tissue growth factor expression in human granulosa cells through Smad and ERK1/2 signaling pathways. PLoS ONE 10(5), e0126532.
| Crossref | Google Scholar |
Cheng J-C, Chang H-M, Leung PCK (2017) Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis. Oncotarget 8(49), 85224-85233.
| Crossref | Google Scholar |
Choi C, Jeong W, Ghang B, Park Y, Hyun C, Cho M, Kim J (2020) Cyr61 synthesis is induced by interleukin-6 and promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Research & Therapy 22(1), 275.
| Crossref | Google Scholar |
Crockett JC, Schütze N, Tosh D, Jatzke S, Duthie A, Jakob F, Rogers MJ (2007) The matricellular protein CYR61 inhibits osteoclastogenesis by a mechanism independent of αvβ3 and αvβ5. Endocrinology 148(12), 5761-5768.
| Crossref | Google Scholar |
Dean RA, Butler GS, Hamma-Kourbali Y, Delbé J, Brigstock DR, Courty J, Overall CM (2007) Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis. Molecular and Cellular Biology 27(24), 8454-8465.
| Crossref | Google Scholar |
de Andrade LG, Portela VM, Dos Santos EC, Aires KdV, Ferreira R, Missio D, da Silva Z, Koch J, Antoniazzi AQ, Gonçalves PBD, Zamberlam G (2022) FSH regulates YAP-TEAD transcriptional activity in bovine granulosa cells to allow the future dominant follicle to exert its augmented estrogenic capacity. International Journal of Molecular Sciences 23(22), 14160.
| Crossref | Google Scholar |
Dos Santos EC, Lalonde-Larue A, Antoniazzi AQ, Barreta MH, Price CA, Dias Gonçalves PB, Portela VM, Zamberlam G (2022) YAP signaling in preovulatory granulosa cells is critical for the functioning of the EGF network during ovulation. Molecular and Cellular Endocrinology 541, 111524.
| Crossref | Google Scholar |
Dos Santos EC, Boyer A, St-Jean G, Jakuc N, Gévry N, Price CA, Zamberlam G (2023) Is the hippo pathway effector yes-associated protein a potential key player of dairy cattle cystic ovarian disease pathogenesis? Animals 13, 2851.
| Crossref | Google Scholar |
Duan G, Ren C, Zhang Y, Feng S (2015) MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1. Tumor Biology 36(8), 6201-6209.
| Crossref | Google Scholar | PubMed |
Duffy DM, Ko C, Jo M, Brannstrom M, Curry TE, Jr. (2019) Ovulation: parallels with inflammatory processes. Endocrine Reviews 40(2), 369-416.
| Crossref | Google Scholar |
Duncan WC, Hillier SG, Gay E, Bell J, Fraser HM (2005) Connective tissue growth factor expression in the human corpus luteum: paracrine regulation by human chorionic gonadotropin. The Journal of Clinical Endocrinology & Metabolism 90(9), 5366-5376.
| Crossref | Google Scholar | PubMed |
Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM (1999) Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Molecular Endocrinology 13(6), 1035-1048.
| Crossref | Google Scholar | PubMed |
Fan Q, Cheng Y, Chang H-M, Deguchi M, Hsueh AJ, Leung PCK (2017) Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling. Oncotarget 8(16), 27166-27176.
| Crossref | Google Scholar |
Feng J, Gou J, Jia J, Yi T, Cui T, Li Z (2016) Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer. OncoTargets and Therapy 9, 5371-5381.
| Crossref | Google Scholar |
Field SL, Dasgupta T, Cummings M, Orsi NM (2014) Cytokines in ovarian folliculogenesis, oocyte maturation and luteinisation. Molecular Reproduction and Development 81(4), 284-314.
| Crossref | Google Scholar |
Gery S, Xie D, Yin D, Gabra H, Miller C, Wang H, Scott D, Yi WS, Popoviciu ML, Said JW, Koeffler HP (2005) Ovarian carcinomas: CCN genes are aberrantly expressed and CCN1 promotes proliferation of these cells. Clinical Cancer Research 11(20), 7243-7254.
| Crossref | Google Scholar | PubMed |
Goulet MR, Hutchings D, Donahue J, Elder D, Tsang PCW (2022) Regulation of cellular communication network factor 1 by Ras homolog family member A in bovine steroidogenic luteal cells. Journal of Animal Science 100(7), skac124.
| Crossref | Google Scholar |
Gray MR, Malmquist JA, Sullivan M, Blea M, Castellot JJ, Jr (2007) CCN5 Expression in mammals. II. Adult rodent tissues. Journal of Cell Communication and Signaling 1(2), 145-158.
| Crossref | Google Scholar | PubMed |
Guo T, Zhang J, Yao W, Du X, Li Q, Huang L, Ma M, Li Q, Liu H, Pan Z (2019) CircINHA resists granulosa cell apoptosis by upregulating CTGF as a ceRNA of miR-10a-5p in pig ovarian follicles. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1862(10), 194420.
| Crossref | Google Scholar |
Habel N, Vilalta M, Bawa O, Opolon P, Blanco J, Fromigué O (2015) Cyr61 silencing reduces vascularization and dissemination of osteosarcoma tumors. Oncogene 34(24), 3207-3213.
| Crossref | Google Scholar | PubMed |
Han P, Relav L, Price CA (2020) Regulation of the early growth response-1 binding protein NAB2 in bovine granulosa cells and effect on connective tissue growth factor expression. Molecular and Cellular Endocrinology 518, 111041.
| Crossref | Google Scholar |
Harlow CR, Bradshaw AC, Rae MT, Shearer KD, Hillier SG (2007) Oestrogen formation and connective tissue growth factor expression in rat granulosa cells. Journal of Endocrinology 192(1), 41-52.
| Crossref | Google Scholar |
Henrot P, Moisan F, Laurent P, Manicki P, Kaulanjan-Checkmodine P, Jolivel V, Rezvani HR, Leroy V, Picard F, Boulon C, Schaeverbeke T, Seneschal J, Lazaro E, Taïeb A, Truchetet M-E, Cario M (2020) Decreased CCN3 in systemic sclerosis endothelial cells contributes to impaired angiogenesis. Journal of Investigative Dermatology 140(7), 1427-1434.e5.
| Crossref | Google Scholar |
Holbourn KP, Acharya KR, Perbal B (2008) The CCN family of proteins: structure-function relationships. Trends in Biochemical Sciences 33(10), 461-473.
| Crossref | Google Scholar |
Hopkins TIR, Bemmer VL, Franks S, Dunlop C, Hardy K, Dunlop IE (2021) Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma. Biomaterials 277, 121099.
| Crossref | Google Scholar |
Hou C-H, Tang C-H, Hsu C-J, Hou S-M, Liu J-F (2013) CCN4 induces IL-6 production through αvβ5 receptor, PI3K, Akt, and NF-κB singling pathway in human synovial fibroblasts. Arthritis Research & Therapy 15(1), R19.
| Crossref | Google Scholar |
Hu L-L, Chang H-M, Yi Y, Liu Y, Taylor EL, Zheng L-P, Leung PCK (2019) CCN2 mediates S1P-induced upregulation of COX2 expression in human granulosa-lutein cells. Cells 8(11), 1445.
| Crossref | Google Scholar |
Huang X, Ni B, Mao Z, Xi Y, Chu X, Zhang R, Ma X, You H (2019) NOV/CCN3 induces cartilage protection by inhibiting PI3K/AKT/mTOR pathway. Journal of Cellular and Molecular Medicine 23(11), 7525-7534.
| Crossref | Google Scholar |
Inoki I, Shiomi T, Hashimoto G, Enomoto H, Nakamura H, Makino K-I, Ikeda E, Takata S, Kobayashi K-I, Okada Y (2002) Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. The FASEB Journal 16(2), 1-27.
| Crossref | Google Scholar |
Jeong D, Lee M-A, Li Y, Yang DK, Kho C, Oh JG, Hong G, Lee A, Song MH, LaRocca TJ, Chen J, Liang L, Mitsuyama S, D’Escamard V, Kovacic JC, Kwak TH, Hajjar RJ, Park WJ (2016) Matricellular protein CCN5 reverses established cardiac fibrosis. Journal of the American College of Cardiology 67(13), 1556-1568.
| Crossref | Google Scholar | PubMed |
Jian Y-C, Wang J-J, Dong S, Hu J-W, Hu L-J, Yang G-M, Zheng Y-X, Xiong W-J (2014) Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo. Clinical Laboratory 60(1), 29-35.
| Crossref | Google Scholar | PubMed |
Joliot V, Martinerie C, Dambrine G, Plassiart G, Brisac M, Crochet J, Perbal B (1992) Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. Molecular and Cellular Biology 12(1), 10-21.
| Crossref | Google Scholar |
Jun J-I, Lau LF (2011) Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nature Reviews Drug Discovery 10(12), 945-963.
| Crossref | Google Scholar | PubMed |
Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho C-H, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ (2013) Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proceedings of the National Academy of Sciences of the United States of America 110(43), 17474-17479.
| Crossref | Google Scholar |
Kim H, Son S, Shin I (2018) Role of the CCN protein family in cancer. BMB Reports 51(10), 486-492.
| Crossref | Google Scholar |
Kleer CG, Zhang Y, Pant Q, Merajver SD (2004) WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer. Neoplasia 6(2), 179-185.
| Crossref | Google Scholar | PubMed |
Koch J, Portela VM, Dos Santos EC, Missio D, de Andrade LG, da Silva Z, Gasperin BG, Antoniazzi AQ, Gonçalves PBD, Zamberlam G (2022) The Hippo pathway effectors YAP and TAZ interact with EGF-like signaling to regulate expansion-related events in bovine cumulus cells in vitro. Journal of Assisted Reproduction and Genetics 39(2), 481-492.
| Crossref | Google Scholar |
Kubota S, Takigawa M (2013) The CCN family acting throughout the body: recent research developments. BioMolecular Concepts 4(5), 477-494.
| Crossref | Google Scholar | PubMed |
Kubota S, Kawata K, Hattori T, Nishida T (2022) Molecular and genetic interactions between CCN2 and CCN3 behind their Yin-Yang collaboration. International Journal of Molecular Sciences 23(11), 5887.
| Crossref | Google Scholar |
Kuwahara M, Kadoya K, Kondo S, Fu S, Miyake Y, Ogo A, Ono M, Furumatsu T, Nakata E, Sasaki T, Minagi S, Takigawa M, Kubota S, Hattori T (2020) CCN3 (NOV) drives degradative changes in aging articular cartilage. International Journal of Molecular Sciences 21(20), 7556.
| Crossref | Google Scholar |
Lake AC, Castellot JJ, Jr (2003) CCN5 modulates the antiproliferative effect of heparin and regulates cell motility in vascular smooth muscle cells. Cell Communication and Signaling : CCS 1(1), 5.
| Crossref | Google Scholar |
Lan H, Dong Z-W, Zhang M-Y, Li W-Y, Chong C-J, Wu Y-Q, Wang Z-X, Liu J-Y, Liu Z-Q, Qin X-H, Jiang T-M, Song J-L (2024) Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats. Food Science & Nutrition 12(4), 2917-2931.
| Crossref | Google Scholar |
Le Dréau G, Kular L, Nicot AB, Calmel C, Melik-Parsadaniantz S, Kitabgi P, Laurent M, Martinerie C (2010) NOV/CCN3 upregulates CCL2 and CXCL1 expression in astrocytes through β1 and β5 integrins. Glia 58(12), 1510-1521.
| Crossref | Google Scholar | PubMed |
Lee K-B, Byun H-J, Park SH, Park C-Y, Lee S-H, Rho SB (2012) CYR61 controls p53 and NF-κB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. Cancer Letters 315(1), 86-95.
| Crossref | Google Scholar | PubMed |
Li J, Ye L, Owen S, Weeks HP, Zhang Z, Jiang WG (2015a) Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (Review). International Journal of Molecular Medicine 36(6), 1451-1463.
| Crossref | Google Scholar |
Li X, Chen Y, Ye W, Tao X, Zhu J, Wu S, Lou L (2015b) Blockade of CCN4 attenuates CCl4-induced liver fibrosis. Archives of Medical Science 11(3), 647-653.
| Crossref | Google Scholar |
Li Y, Wang F, Liu T, Lv N, Yuan X, Li P (2022) WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis. Journal of Ovarian Research 15(1), 94.
| Crossref | Google Scholar |
Lin CG, Leu S-J, Chen N, Tebeau CM, Lin S-X, Yeung C-Y, Lau LF (2003) CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. Journal of Biological Chemistry 278(26), 24200-24208.
| Crossref | Google Scholar |
Lin J, Zhou Z, Huo R, Xiao L, Ouyang G, Wang L, Sun Y, Shen B, Li D, Li N (2012) Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis. The Journal of Immunology 188(11), 5776-5784.
| Crossref | Google Scholar |
Liu J, Kosma V-M, Vänttinen T, Hydén-Granskog C, Voutilainen R (2002) Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells. Molecular Human Reproduction 8(2), 136-141.
| Crossref | Google Scholar |
Liu S-C, Hsu C-J, Fong Y-C, Chuang S-M, Tang C-H (2013) CTGF induces monocyte chemoattractant protein-1 expression to enhance monocyte migration in human synovial fibroblasts. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833(5), 1114-1124.
| Crossref | Google Scholar | PubMed |
Liu Y, Song Y, Ye M, Hu X, Wang ZP, Zhu X (2019a) The emerging role of WISP proteins in tumorigenesis and cancer therapy. Journal of Translational Medicine 17(1), 28.
| Crossref | Google Scholar |
Liu S, Chang H-M, Yi Y, Yao Y-Q, Leung PCK (2019b) SMAD-dependent signaling mediates morphogenetic protein 6-induced stimulation of connective tissue growth factor in luteinized human granulosa cells. Biology of Reproduction 101(2), 445-456.
| Crossref | Google Scholar |
Malik AR, Liszewska E, Jaworski J (2015) Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system. Frontiers in Cellular Neuroscience 9, 237.
| Crossref | Google Scholar |
Miao ZL, Guo L, Wang YX, Cui R, Yang N, Huang MQ, Qin WB, Chen J, Li HM, Wang ZN, Wei XC (2012) The intervention effect of Rosiglitozone in ovarian fibrosis of PCOS rats. Biomedical and Environmental Sciences 25(1), 46-52.
| Crossref | Google Scholar |
Morgan RJ, Jr., Alvarez RD, Armstrong DK, Boston B, Burger RA, Chen L-M, Copeland L, Crispens MA, Gershenson D, Gray HJ, Grigsby PW, Hakam A, Havrilesky LJ, Johnston C, Lele S, Matulonis UA, O’Malley DM, Penson RT, Remmenga SW, Sabbatini P, Schilder RJ, Schink JC, Teng N, Werner TL (2011) Epithelial ovarian cancer. Journal of the National Comprehensive Cancer Network 9(1), 82-113.
| Crossref | Google Scholar | PubMed |
Moussad EE-DA, Brigstock DR (2000) Connective tissue growth factor: what’s in a name? Molecular Genetics and Metabolism 71(1-2), 276-292.
| Crossref | Google Scholar |
Nagashima T, Kim J, Li Q, Lydon JP, DeMayo FJ, Lyons KM, Matzuk MM (2011) Connective tissue growth factor is required for normal follicle development and ovulation. Molecular Endocrinology 25(10), 1740-1759.
| Crossref | Google Scholar |
O’Brien TP, Yang GP, Sanders L, Lau LF (1990) Expression of cyr61, a growth factor-inducible immediate-early gene. Molecular and Cellular Biology 10(7), 3569-3577.
| Crossref | Google Scholar |
Parrott JA, Skinner MK (1998) Developmental and hormonal regulation of hepatocyte growth factor expression and action in the bovine ovarian follicle. Biology of Reproduction 59(3), 553-560.
| Crossref | Google Scholar |
Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ (1998) WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proceedings of the National Academy of Sciences of the United States of America 95(25), 14717-14722.
| Crossref | Google Scholar |
Phan B, Rakenius A, Pietrowski D, Bettendorf H, Keck C, Herr D (2006) hCG-dependent regulation of angiogenic factors in human granulosa lutein cells. Molecular Reproduction and Development 73(7), 878-884.
| Crossref | Google Scholar |
Richards JS (2018) From follicular development and ovulation to ovarian cancers: an unexpected journey. Vitamins and Hormones 107, 453-472.
| Crossref | Google Scholar | PubMed |
Sánchez-López E, Rayego S, Rodrigues-Díez R, Rodriguez JS, Rodrigues-Díez R, Rodríguez-Vita J, Carvajal G, Aroeira LS, Selgas R, Mezzano SA, Ortiz A, Egido J, Ruiz-Ortega M (2009) CTGF promotes inflammatory cell infiltration of the renal interstitium by activating NF-κB. Journal of the American Society of Nephrology 20(7), 1513-1526.
| Crossref | Google Scholar |
Schindler R, Nilsson E, Skinner MK (2010) Induction of ovarian primordial follicle assembly by connective tissue growth factor CTGF. PLoS ONE 5(9), e12979.
| Crossref | Google Scholar |
Shi Z-Q, Chen Z-Y, Han Y, Zhu H-Y, Lyu M-D, Zhang H, Zhang Y, Yang L-Q, Pan W-W (2020) WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells. Journal of Ovarian Research 13(1), 85.
| Crossref | Google Scholar |
Shimbo A, Kajiyama H, Tamauchi S, Yoshikawa N, Ikeda Y, Nishino K, Suzuki S, Niimi K, Sakata J, Kikkawa F (2019) Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma. Oncology Reports 42(6), 2323-2332.
| Crossref | Google Scholar |
Silva ESd, Amaral C, Barreta M, Antoniazzi A, Andrade LGd, Ferreira R, Mesquita F, Portela VM, Gonçalves PB (2022) FGF18 modulates CTGF mRNA expression in cumulus-oocyte complexes and early bovine embryos: preliminary data. Zygote 30(2), 239-243.
| Crossref | Google Scholar | PubMed |
Slee RB, Hillier SG, Largue P, Harlow CR, Miele G, Clinton M (2001) Differentiation-dependent expression of connective tissue growth factor and lysyl oxidase messenger ribonucleic acids in rat granulosa cells. Endocrinology 142(3), 1082-1089.
| Crossref | Google Scholar |
Son S, Kim H, Lim H, Lee J-H, Lee K-M, Shin I (2023) CCN3/NOV promotes metastasis and tumor progression via GPNMB-induced EGFR activation in triple-negative breast cancer. Cell Death & Disease 14(2), 81.
| Crossref | Google Scholar |
Spicer LJ, Schutz LF, Aad PY (2021) Effects of bone morphogenetic protein 4, gremlin, and connective tissue growth factor on estradiol and progesterone production by bovine granulosa cells. Journal of Animal Science 99(11), skab318.
| Crossref | Google Scholar |
Sriraman V, Eichenlaub-Ritter U, Bartsch JW, Rittger A, Mulders SM, Richards JS (2008) Regulated expression of ADAM8 (a disintegrin and metalloprotease domain 8) in the mouse ovary: evidence for a regulatory role of luteinizing hormone, progesterone receptor, and epidermal growth factor-like growth factors. Biology of Reproduction 78(6), 1038-1048.
| Crossref | Google Scholar |
Sun X, Yan X, Liu K, Wu M, Li Z, Wang Y, Zhong X, Qin L, Huang C, Wei X (2020) lncRNA H19 acts as a ceRNA to regulate the expression of CTGF by targeting miR-19b in polycystic ovary syndrome. Brazilian Journal of Medical and Biological Research 53(11), e9266.
| Crossref | Google Scholar |
Sun C, Zhang H, Liu X (2021) Emerging role of CCN family proteins in fibrosis. Journal of Cellular Physiology 236(6), 4195-4206.
| Crossref | Google Scholar |
Tan G, Cao X, Dai Q, Zhang B, Huang J, Xiong S, Zhang YY, Chen W, Yang J, Li H (2015) A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ. Oncotarget 6(11), 8676-8686.
| Crossref | Google Scholar |
Tsai H-C, Su H-L, Huang C-Y, Fong Y-C, Hsu C-J, Tang C-H (2014) CTGF increases matrix metalloproteinases expression and subsequently promotes tumor metastasis in human osteosarcoma through down-regulating miR-519d. Oncotarget 5(11), 3800-3812.
| Crossref | Google Scholar |
Tsai H-C, Tzeng H-E, Huang C-Y, Huang Y-L, Tsai C-H, Wang S-W, Wang P-C, Chang A-C, Fong Y-C, Tang C-H (2017) WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma. Cell Death & Disease 8(4), e2750.
| Crossref | Google Scholar |
Wandji S-A, Gadsby JE, Barber JA, Hammond JM (2000) Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis. Endocrinology 141(7), 2648-2657.
| Crossref | Google Scholar |
Wang X, McLennan SV, Allen TJ, Twigg SM (2010) Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes. Journal of Cell Communication and Signaling 4(1), 15-23.
| Crossref | Google Scholar |
Wang F, Zhang Z-F, He Y-R, Wu H-Y, Wei S-S (2019) Effects of dipeptidyl peptidase-4 inhibitors on transforming growth factor-β1 signal transduction pathways in the ovarian fibrosis of polycystic ovary syndrome rats. Journal of Obstetrics and Gynaecology Research 45(3), 600-608.
| Crossref | Google Scholar | PubMed |
Wells JE, Howlett M, Cheung LC, Kees UR (2015) The role of CCN family genes in haematological malignancies. Journal of Cell Communication and Signaling 9(3), 267-278.
| Crossref | Google Scholar | PubMed |
Winterhager E, Gellhaus A (2014) The role of the CCN family of proteins in female reproduction. Cellular and Molecular Life Sciences 71(12), 2299-2311.
| Crossref | Google Scholar |
Wu C-L, Tsai H-C, Chen Z-W, Wu C-M, Li T-M, Fong Y-C, Tang C-H (2013) Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma. Cellular Signalling 25(12), 2812-2822.
| Crossref | Google Scholar | PubMed |
Yang L, Hou J, Cui X-H, Suo L-N, Lv Y-W (2017) MiR-133b regulates the expression of CTGF in epithelial-mesenchymal transition of ovarian cancer. European Review for Medical and Pharmacological Sciences 21(24), 5602-5609.
| Crossref | Google Scholar |
Yoon PO, Lee M-A, Cha H, Jeong MH, Kim J, Jang SP, Choi BY, Jeong D, Yang DK, Hajjar RJ, Park WJ (2010) The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis. Journal of Molecular and Cellular Cardiology 49(2), 294-303.
| Crossref | Google Scholar | PubMed |
Zhang B, Tsang PCW, Pate JL, Moses MA (2011) A role for cysteine-rich 61 in the angiogenic switch during the estrous cycle in cows: regulation by prostaglandin F2alpha. Biology of Reproduction 85(2), 261-268.
| Crossref | Google Scholar |
Zhang X, Zhang C, Shen S, Xia YJ, Yi L, Gao Q, Wang Y (2013) Dehydroepiandrosterone induces ovarian and uterine hyperfibrosis in female rats. Human Reproduction 28(11), 3074-3085.
| Crossref | Google Scholar |
Zhang H, Li W, Huang P, Lin L, Ye H, Lin D, Koeffler HP, Wang J, Yin D (2015) Expression of CCN family members correlates with the clinical features of hepatocellular carcinoma. Oncology Reports 33(3), 1481-1492.
| Crossref | Google Scholar |
Zhang X-Y, Chang H-M, Yi Y, Zhu H, Liu R-Z, Leung PCK (2021) BMP6 increases CD68 expression by up-regulating CTGF expression in human granulosa-lutein cells. Molecular and Cellular Endocrinology 536, 111414.
| Crossref | Google Scholar |
Zhou Y-Y, He C-H, Lan H, Dong Z-W, Wu Y-Q, Song J-L (2022) Rhamnocitrin decreases fibrosis of ovarian granulosa cells by regulating the activation of the PPARγ/NF-κB/TGF-β1/Smad2/3 signaling pathway mediated by Wisp2. Annals of Translational Medicine 10(14), 789.
| Crossref | Google Scholar |
Zhou Y-Y, Wu Y-Q, Chong C-J, Zhong S-M, Wang Z-X, Qin X-H, Liu Z-Q, Liu J-Y, Song J-L (2023) Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-β1/smad pathway. Heliyon 9(8), e18741.
| Crossref | Google Scholar |
Zhu Y (2021) Metalloproteases in gonad formation and ovulation. General and Comparative Endocrinology 314, 113924.
| Crossref | Google Scholar |
Zhu G, Mao Y, Zhou W, Jiang Y (2015) Dynamic changes in the follicular transcriptome and promoter DNA Methylation pattern of steroidogenic genes in chicken follicles throughout the ovulation cycle. PLoS ONE 10(12), e0146028.
| Crossref | Google Scholar |