Transition of autophagy and apoptosis in fibroblasts depends on dominant expression of HIF-1α or p53.
- Author:
Min LI
1
;
Yidan SU
2
;
Xiaoyuan GAO
1
;
Jiarong YU
1
;
Zhiyong WANG
3
;
Xiqiao WANG
4
Author Information
- Publication Type:Journal Article
- Keywords: Apoptosis; Autophagy; Hypertrophic scar; Hypoxia-inducible factor-1α (HIF-1α); p53
- MeSH: Apoptosis; Autophagy; Cell Hypoxia; Fibroblasts/metabolism*; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*; Tumor Suppressor Protein p53/metabolism*
- From: Journal of Zhejiang University. Science. B 2022;23(3):204-217
- CountryChina
- Language:English
- Abstract: 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-1α and 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-1α or p53 gene expression or triggered overexpression to investigate the changes of HIF-1α and 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-1α expression increased in parallel with autophagosome formation. Under hypoxia, HIF-1α expression 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-1α and p53, which is linked with scar hyperplasia and regression.
