FGF9 promotes mouse spermatogonial stem cell proliferation mediated by p38 MAPK signalling.

Autor: Yang F; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Whelan EC; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Guan X; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China., Deng B; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China., Wang S; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China., Sun J; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China., Avarbock MR; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Wu X; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China., Brinster RL; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2021 Jan; Vol. 54 (1), pp. e12933. Date of Electronic Publication: 2020 Oct 26.
DOI: 10.1111/cpr.12933
Abstrakt: Objectives: Fibroblast growth factor 9 (FGF9) is expressed by somatic cells in the seminiferous tubules, yet little information exists about its role in regulating spermatogonial stem cells (SSCs).
Materials and Methods: Fgf9 overexpression lentivirus was injected into mouse testes, and PLZF immunostaining was performed to investigate the effect of FGF9 on spermatogonia in vivo. Effect of FGF9 on SSCs was detected by transplanting cultured germ cells into tubules of testes. RNA-seq of bulk RNA and single cell was performed to explore FGF9 working mechanisms. SB203580 was used to disrupt p38 MAPK pathway. p38 MAPK protein expression was detected by Western blot and qPCR was performed to determine different gene expression. Small interfering RNA (siRNA) was used to knock down Etv5 gene expression in germ cells.
Results: Overexpression of Fgf9 in vivo resulted in arrested spermatogenesis and accumulation of undifferentiated spermatogonia. Exposure of germ cell cultures to FGF9 resulted in larger numbers of SSCs over time. Inhibition of p38 MAPK phosphorylation negated the SSC growth advantage provided by FGF9. Etv5 and Bcl6b gene expressions were enhanced by FGF9 treatment. Gene knockdown of Etv5 disrupted the growth effect of FGF9 in cultured SSCs along with downstream expression of Bcl6b.
Conclusions: Taken together, these data indicate that FGF9 is an important regulator of SSC proliferation, operating through p38 MAPK phosphorylation and upregulating Etv5 and Bcl6b in turn.
(© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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