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Publication : Proteasome activator REGγ promotes inflammation in Leydig cells via IkBε signaling.

First Author  Xie T Year  2019
Journal  Int J Mol Med Volume  43
Issue  5 Pages  1961-1968
PubMed ID  30816488 Mgi Jnum  J:292145
Mgi Id  MGI:6445000 Doi  10.3892/ijmm.2019.4115
Citation  Xie T, et al. (2019) Proteasome activator REGgamma promotes inflammation in Leydig cells via IkBepsilon signaling. Int J Mol Med 43(5):1961-1968
abstractText  The development of testicular inflammation affects the normal male reproductive function. The proteasome activator complex subunit 3 (REGgamma) has been suggested to regulate experimental colitis. However, to the best of our knowledge, a potential association between REGgamma and testicular inflammation has not been demonstrated. The present study successfully established inflammatory models in C57 mice, primary Leydig cells and the TM3 cell line. It was observed that the absence of REGgamma conveyed a significantly protective effect toward testosterone secretion in Leydig cells. REGgamma deficiency significantly decreased the expression levels of phosphorylated transcription factor p65 and inflammatory factors in testis tissues, primary Leydig cells and the TM3 cell line. Inflammation also upregulated the expression levels of REGgamma. Furthermore, the degradation of the nuclear factor lightchainenhancer of activated B cells (NFkappaB) inhibitor epsilon (IkBepsilon) signaling pathway regulated REGgamma and NFkappaB expression. Double knockdown of REGgamma and IkBepsilon restored the response in wildtype cells to LPSinduced inflammation. In summary, these results demonstrated that REGgamma regulates NFkappaB activity by specifically degrading IkBepsilon to regulate inflammation in testicular Leydig cells.
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