ArticleReproductive biology and endocrinology : RB&E2022
Connective tissue growth factor mediates bone morphogenetic protein 2-induced increase in hyaluronan production in luteinized human granulosa cells.
Article in Reproductive biology and endocrinology : RB&E, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 5 citations in OpenAlex.
- [Role of hyaluronic acid synthases in female infertility-related diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- A Systematic Review and Integrated Bioinformatic Analysis on the Gene Expression of Cumulus-Oocyte Complex Following In Vitro Maturation.The Malaysian journal of medical sciences : MJMS · 2025Review
- Bone morphogenetic protein 6 induces downregulation of pentraxin 3 expression in human granulosa lutein cells in women with polycystic ovary syndrome.Journal of assisted reproduction and genetics · 2024Article
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4 authors at 2 institutions in 3 countries.
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Abstract
backgroundHyaluronan is the main component of the cumulus-oocyte complex (COC) matrix, and it maintains the basic structure of the COC during ovulation. As a member of the transforming growth factor β (TGF-β) superfamily, bone morphogenetic protein 2 (BMP2) has been identified as a critical regulator of mammalian folliculogenesis and ovulation. However, whether BMP2 can regulate the production of hyaluronan in human granulosa cells has never been elucidated.
methodsIn the present study, we investigated the effect of BMP2 on the production of hyaluronan and the underlying molecular mechanism using both immortalized (SVOG) and primary human granulosa-lutein (hGL) cells. The expression of three hyaluronan synthases (including HAS1, HAS2 and HAS3) were examined following cell incubation with BMP2 at different concentrations. The concentrations of the hyaluronan cell culture medium were determined by enzyme-linked immunosorbent assay (ELISA). The TGF-β type I receptor inhibitors (dorsomorphin and DMH-1) and small interfering RNAs targeting ALK2, ALK3, ALK6 and SMAD4 were used to investigate the involvement of TGF-β type I receptor and SMAD-dependent pathway.
resultsOur results showed that BMP2 treatment significantly increased the production of hyaluronan by upregulating the expression of hyaluronan synthase 2 (HAS2). In addition, BMP2 upregulates the expression of connective tissue growth factor (CTGF), which subsequently mediates the BMP2-induced increases in HAS2 expression and hyaluronan production because overexpression of CTGF enhances, whereas knockdown of CTGF reverses, these effects. Notably, using kinase inhibitor- and siRNA-mediated knockdown approaches, we demonstrated that the inductive effect of BMP2 on the upregulation of CTGF is mediated by the ALK2/ALK3-mediated SMAD-dependent signaling pathway.
conclusionsOur findings provide new insight into the molecular mechanism by which BMP2 promotes the production of hyaluronan in human granulosa cells.
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