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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2100187


Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53


Author(s):  Min LI, Yidan SU, Xiaoyuan GAO, Jiarong YU, Zhiyong WANG and Xiqiao WANG

Affiliation(s):  Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; more

Corresponding email(s):   wxqiao2002@hotmail.com, wzy10830@rjh.com.cn

Key Words:  Hypertrophic scar, HIF-1&alpha


Min LI, Yidan SU, Xiaoyuan GAO, Jiarong YU, Zhiyong WANG and Xiqiao WANG. Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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author="Min LI, Yidan SU, Xiaoyuan GAO, Jiarong YU, Zhiyong WANG and Xiqiao WANG",
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%T Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53
%A Min LI
%A Yidan SU
%A Xiaoyuan GAO
%A Jiarong YU
%A Zhiyong WANG and Xiqiao WANG
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
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T1 - Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53
A1 - Min LI
A1 - Yidan SU
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J0 - Journal of Zhejiang University Science B
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2100187


Abstract: 
It has been revealed that hypoxia is dynamic in hypertrophic scars, therefore, we considered that it may have different effects on HIF-1&alpha; and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1&alpha; and p53 that is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1&alpha; and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1&alpha; or p53 gene expression or triggered overexpression to investigate the changes of HIF-1&alpha; and p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1&alpha;, p53 and autophagy-related proteins were assayed using western blot and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using CCK-8 and BrdU staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1&alpha; and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1&alpha; expression increases in parallel with autophagosome formation. Under hypoxia, HIF-1&alpha; expression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1&alpha; knockdown downregulated autophagy, proliferation, p300-bound HIF-1&alpha;, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1&alpha;, whereas p53 overexpression resulted in the same effects and reduced HIF-1&alpha;. Our results suggest a teeterboard-like conversion between HIF-1&alpha; and p53, which is linked with scar hyperplasia and regression.

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