BMP6 Regulates Proliferation and Apoptosis of Human Sertoli Cells Via Smad2/3 and Cyclin D1 Pathway and DACH1 and TFAP2A Activation
| Autor: | Liping Wen, Ruinan Shen, Qingqing Yuan, Qisheng Lin, Ruobing Jia, Chencheng Yao, Fan Zhou, Wenjie Liu, Hongyong Fu, Minghui Niu, Zheng Li, Zuping He, Zheng Chen, Min Sun, Hong Wang, Jingmei Hou |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Transcriptional Activation 0301 basic medicine endocrine system Bone Morphogenetic Protein 6 Apoptosis Smad Proteins Smad2 Protein Article 03 medical and health sciences 0302 clinical medicine Cyclin D1 Annexin medicine Humans Smad3 Protein Phosphorylation Eye Proteins Cells Cultured Cell Proliferation Sertoli Cells Multidisciplinary urogenital system Chemistry Cell growth Sertoli cell Cell biology 030104 developmental biology medicine.anatomical_structure Transcription Factor AP-2 030220 oncology & carcinogenesis Signal transduction Spermatogenesis Cyclin A2 Signal Transduction Transcription Factors |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Sertoli cells are essential for regulating normal spermatogenesis. However, the mechanisms underlying human Sertoli cell development remain largely elusive. Here we examined the function and signaling pathways of BMP6 in regulating human Sertoli cells. RT-PCR, immunocytochemistry and Western blots revealed that BMP6 and its multiple receptors were expressed in human Sertoli cells. CCK-8 and EDU assays showed that BMP6 promoted the proliferation of Sertoli cells. Conversely, BMP6 siRNAs inhibited the division of these cells. Annexin V/PI assay indicated that BMP6 reduced the apoptosis in human Sertoli cells, whereas BMP6 knockdown assumed reverse effects. BMP6 enhanced the expression levels of ZO1, SCF, GDNF and AR in human Sertoli cells, and ELISA assay showed an increase of SCF by BMP6 and a reduction by BMP6 siRNAs. Notably, Smad2/3 phosphorylation and cyclin D1 were enhanced by BMP6 and decreased by BMP6 siRNAs in human Sertoli cells. The levels of DACH1 and TFAP2A were increased by BMP6 and reduced by BMP6 siRNAs, and the growth of human Sertoli cells was inhibited by these siRNAs. Collectively, these results suggest that BMP6 regulates the proliferation and apoptosis of human Sertoli cells via activating the Smad2/3/cyclin D1 and DACH1 and TFAP2A pathway. |
| Databáze: | OpenAIRE |
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