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

• 作者: Min LI Yidan SU Xiaoyuan GAO Jiarong YU Zhiyong WANG Xiqiao WANG
• 来源期刊: 浙江大学学报（英文版）（B辑：生物医学和生物技术）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Research Articles
• 页码范围: 204-217,中插1
• 页数: 15页
• 语种: 英文

摘要

It has been revealed that hypoxia is dynamic in hypertrophic scars;therefore, we considered that it may have different effects on hypoxia-inducible factor-1α(HIF-1α) and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1αand p53, which is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1α and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1αor p53 gene expression or triggered overexpression to investigate the changes of HIF-1αand p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1α, p53, and autophagy-related proteins were assayed using western blotting and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using cell counting kit-8 (CCK-8) and 5-bromo-2'-deoxyuridine (BrdU) staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1α and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1αexpression increased in parallel with autophagosome formation. Under hypoxia, HIF-1αexpression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1α knockdown downregulated autophagy, proliferation, and p300-bound HIF-1α, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1α, whereas p53 overexpression resulted in the same effects and reduced HIF-1α. Our results suggest a teeterboard-like conversion between HIF-1αand p53, which is linked with scar hyperplasia and regression.