RhoA promotes epidermal stem cell proliferation via PKN1-cyclin D1 signalingReport as inadecuate




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Objective

Epidermal stem cells ESCs play a critical role in wound healing, but the mechanism underlying ESC proliferation is not well defined. Here, we explore the effects of RhoA on ESC proliferation and the possible underlying mechanism.

Methods

Human ESCs were enriched by rapid adhesion to collagen IV. RhoA+-+G14V, RhoA-T19N and pGFP control plasmids were transfected into human ESCs. The effect of RhoA on cell proliferation was detected by cell proliferation and DNA synthesis assays. Induction of PKN1 activity by RhoA was determined by immunoblot analysis, and the effects of PKN1 on RhoA in terms of inducing cell proliferation and cyclin D1 expression were detected using specific siRNA targeting PKN1. The effects of U-46619 a RhoA agonist and C3 transferase a RhoA antagonist on ESC proliferation were observed in vivo.

Results

RhoA had a positive effect on ESC proliferation, and PKN1 activity was up-regulated by the active RhoA mutant G14V and suppressed by RhoA T19N. Moreover, the ability of RhoA to promote ESC proliferation and DNA synthesis was interrupted by PKN1 siRNA. Additionally, cyclin D1 protein and mRNA expression levels were up-regulated by RhoA G14V, and these effects were inhibited by siRNA-mediated knock-down of PKN1. RhoA also promoted ESC proliferation via PKN in vivo.

Conclusion

This study shows that the effect of RhoA on ESC proliferation is mediated by activation of the PKN1-cyclin D1 pathway in vitro, suggesting that RhoA may serve as a new therapeutic target for wound healing.



Author: Fan Wang, Rixing Zhan, Liang Chen, Xia Dai, Wenping Wang, Rui Guo, Xiaoge Li, Zhe Li, Liang Wang, Shupeng Huang, Jie Shen, Shiron

Source: http://plos.srce.hr/



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