Inhbb-KO Mouse

Inhbb, encoding the inhibin βB subunit, is involved in forming protein members of the TGF-β superfamily. This superfamily is extensively involved in cell proliferation, differentiation, adhesion, movement, metabolism, communication, and death. Activins and inhibins, part of this superfamily, were first discovered in ovarian follicular fluid and initially described as regulators of pituitary follicle-stimulating hormone (FSH) secretion [2].

In a mouse model, a variant (c.1079T > C:p.Met360Thr) in Inhbb led to significantly larger testes due to increased Sertoli cell and round spermatid number, with reduced circulating levels of activin B but normal fertility [5]. In renal fibrosis models, inhibiting Inhbb blocked interstitial fibroblast activation and ameliorated renal fibrosis, while its overexpression activated fibroblasts. The upregulation of Inhbb in injured tubular epithelial cells depends on the transcription factor Sox9 [1]. In hepatocellular carcinoma, the Sox9/Inhbb axis promotes tumor growth and metastasis by activating peri-tumoral hepatic stellate cells [4]. In endometrial tissue of recurrent implantation failure patients, downregulated Inhbb impeded decidualization through the ADCY1/cAMP signalling pathway [3].

In conclusion, Inhbb plays diverse roles in multiple biological processes and disease conditions. Mouse models, like the one with the Inhbb gene variant, have revealed its impact on testis composition. Inhbb is also implicated in renal fibrosis, cancer metastasis, and endometrial decidualization, highlighting its importance as a potential therapeutic target in these disease areas.

References:

1. Sun, Yanyan, Cai, Huimin, Ge, Jia, Zhang, Junfeng, Zang, Yuhui. 2021. Tubule-derived INHBB promotes interstitial fibroblast activation and renal fibrosis. In The Journal of pathology, 256, 25-37. doi:10.1002/path.5798. https://pubmed.ncbi.nlm.nih.gov/34543458/

2. Liu, Ying, Zhou, Qing, Zou, Guoying, Zhang, Wenling. 2024. Inhibin subunit beta B (INHBB): an emerging role in tumor progression. In Journal of physiology and biochemistry, 80, 775-793. doi:10.1007/s13105-024-01041-y. https://pubmed.ncbi.nlm.nih.gov/39183219/

3. Zhang, Hui, Wang, Zhilong, Zhou, Quan, Yan, Guijun, Sun, Haixiang. 2023. Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway. In Journal of assisted reproduction and genetics, 40, 1135-1146. doi:10.1007/s10815-023-02762-7. https://pubmed.ncbi.nlm.nih.gov/36913138/

4. Chen, Yu, Qian, Baowei, Sun, Xiaolin, Zhang, Junfeng, Zang, Yuhui. 2020. Sox9/INHBB axis-mediated crosstalk between the hepatoma and hepatic stellate cells promotes the metastasis of hepatocellular carcinoma. In Cancer letters, 499, 243-254. doi:10.1016/j.canlet.2020.11.025. https://pubmed.ncbi.nlm.nih.gov/33246092/

5. Houston, Brendan J, O'Connor, Anne E, Wang, Degang, O'Bryan, Moira K, Walton, Kelly. . Human INHBB Gene Variant (c.1079T>C:p.Met360Thr) Alters Testis Germ Cell Content, but Does Not Impact Fertility in Mice. In Endocrinology, 163, . doi:10.1210/endocr/bqab269. https://pubmed.ncbi.nlm.nih.gov/35022746/