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A Study of HOXA5 Function in Regulating Fibroblasts Activity from Pathological Scars



Liang Yimin, Zhou Renpeng, Yang Yiyuan, Chen Jialin, Wang Danru*

(Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China)
Abstract:

The study is aimed to detect the HOXA5 function in regulating the activity of fibroblasts from pathological scars and p53 pathway. Fibroblasts harvest from both hypertrophic scars (HSFb) and keloids (KFb) transfected with HOXA5-overexpressing plasmids, and were then detected for the ability of proliferation, migration and contraction. Apoptosis was also evaluated. Protein contents of α-SMA, vinculin, Col1A1 and Col3A1were measured. We further detected the combination of HOXA5 with p53 at the hox core motif. Protein contents of p21 and MDm2, the downstream targets of p53 were also measured. As a result, we demonstrated that HOXA5 promoted the apoptosis of both HSFb and KFb, inhibited their proliferation, migration and contraction. Further study through ChIP PCR demonstrated that HOXA5 transactivated p53 expression by combining ATTA-rich core sequence at the promoter site for HOX binding. HOXA5 was also proved to be able to induce the expression of p21 and MDm2. Our results suggest that HOXA5 is able to activate p53 pathway in both HSFb and KFb, promotes cells apoptosis, and inhibits their proliferation, migration and contraction.



CSTR: 32200.14.cjcb.2019.06.0009