Histone lactylation regulates autophagy of hyperplastic scar fibroblasts by inhibiting the transcriptional activity of phosphatase and tensin homologue.

IF 3.8 3区 医学 Q2 CELL BIOLOGY
Wound Repair and Regeneration Pub Date : 2024-09-01 Epub Date: 2024-05-19 DOI:10.1111/wrr.13188
Xiaosong Liu, Biao Wang
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引用次数: 0

Abstract

Hyperplastic scar (HS) is an overreaction of tissue to skin injury caused by local fibroblast proliferation and excessive collagen production. Histone posttranslational modification patterns are important epigenetic processes that control various biological activities. This study was designed to investigate the effects of histone lactylation on HS and the underlying mechanism. Western blot was used to analyse the lactylation level in HS patients and fibroblasts (HSFs). In vitro experiments, western blot, cell counting kit-8, and immunofluorescence staining were performed to detect the collagen level, cell viability, and autophagy, respectively. The relationship between snai2 (SLUG) and phosphatase and tensin homologue (PTEN) was assessed by RNA immunoprecipitation and dual-luciferase reporter assays. The results showed that the histone lactylation level was upregulated in HS tissues and HSFs. HSFs showed increased collagen production and cell viability, and decreased autophagy. Silencing of lactate dehydrogenase A (LDHA) promoted the transcription of PTEN by inhibiting SLUG, thus promoting autophagy. Knockdown of LDHA inhibited collagen deposition and cell viability, and increased autophagy in HSFs, and the results were reversed after PTEN inhibition. In summary, histone lactylation inhibited the transcription activity of PTEN by promoting SLUG, thereby suppressing autophagy and promoting collagen deposition and cell viability of HSFs, which might provide effective therapeutic strategies in HS.

组蛋白乳酰化通过抑制磷酸酶和天丝同源物的转录活性调节增生瘢痕成纤维细胞的自噬。
增生性疤痕(HS)是由于局部成纤维细胞增殖和胶原蛋白过度增生造成的皮肤损伤后组织的过度反应。组蛋白翻译后修饰模式是控制各种生物活动的重要表观遗传过程。本研究旨在探讨组蛋白乳酰化对 HS 的影响及其内在机制。研究采用Western印迹法分析HS患者和成纤维细胞(HSFs)的乳酸化水平。在体外实验中,通过 Western 印迹、细胞计数试剂盒-8 和免疫荧光染色分别检测胶原蛋白水平、细胞活力和自噬。通过RNA免疫沉淀和双荧光素酶报告实验评估了snai2(SLUG)与磷酸酶和天丝同源物(PTEN)之间的关系。结果显示,组蛋白乳化水平在 HS 组织和 HSFs 中上调。HSFs 的胶原蛋白生成和细胞活力增加,自噬功能降低。沉默乳酸脱氢酶A(LDHA)可通过抑制SLUG促进PTEN的转录,从而促进自噬。在 HSFs 中,敲除 LDHA 可抑制胶原沉积和细胞活力,增加自噬,而在抑制 PTEN 后结果逆转。综上所述,组蛋白乳酰化通过促进SLUG抑制了PTEN的转录活性,从而抑制了HSFs的自噬,促进了胶原沉积和细胞活力,这可能会为HS提供有效的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Wound Repair and Regeneration
Wound Repair and Regeneration 医学-皮肤病学
CiteScore
5.90
自引率
3.40%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Wound Repair and Regeneration provides extensive international coverage of cellular and molecular biology, connective tissue, and biological mediator studies in the field of tissue repair and regeneration and serves a diverse audience of surgeons, plastic surgeons, dermatologists, biochemists, cell biologists, and others. Wound Repair and Regeneration is the official journal of The Wound Healing Society, The European Tissue Repair Society, The Japanese Society for Wound Healing, and The Australian Wound Management Association.
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