RBM3 通过 ERK1/2 信号加速糖尿病皮肤伤口愈合。

RBM3 Accelerates Wound Healing of Skin in Diabetes through ERK1/2 Signaling.

机构信息

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, China.

Affiliated Xinhui Hospital, Southern Medical University (People's Hospital of Xinhui District), Jiangmen, China.

出版信息

Curr Mol Pharmacol. 2024;17(1):e18761429260980. doi: 10.2174/0118761429260980231005105929.

DOI:10.2174/0118761429260980231005105929

PMID:37982286

Abstract

BACKGROUND

With the increasing risk of infections and other serious complications, the underlying molecular mechanism of wound healing impairment in diabetes deserves attention. Cold shock proteins (CSPs), including CIRP and RBM3 are highly expressed in the skin; however, it is unknown whether CSPs are involved in the wound-healing impairment of diabetic skin.

OBJECTIVES

The objective of this study is to investigate the effects of RBM3 on skin wound healing in diabetes.

METHODS

In vitro experiments, western blot assay was used to test the levels of proteins in HaCaT cells treated with different concentrations of glucose. RBM3 was over-expressed in HaCaT cells using lentivirus particles. Cell viability was analyzed by Cell-Counting Kit-8 assay and colony formation assay. The migration of HaCaT cells at different concentrations of glucose was evaluated by wound healing assay. In vivo experiments, the mouse model of diabetes was established by intraperitoneal injection of streptozotocin. Four weeks later, the mice were anesthetized by intraperitoneal injection of pentobarbital sodium for skin tissue collection or wound healing experiments. RBM3 knockout mice were established by removing exons 2-6 using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technique and then used in skin wound healing experiments with or without diabetic stress.

RESULTS

In this study, the expression of RBM3, rather than CIRP, was altered in the skin of diabetic specimens, and the RBM3's overexpression accelerated the cell viability and proliferation of HaCaT cells under high glucose conditions. RBM3 deficiency caused delayed wound healing in RBM3 knockout in diabetic conditions. Moreover. RBM3 enhanced the ERK1/2 signaling pathway, and its inhibitor FR180204 blocked the beneficial effect of RBM3 overexpression on skin wound healing in diabetes.

CONCLUSION

RBM3 activated the ERK1/2 signal to facilitate skin wound healing in diabetes, offering a novel therapeutic target for its treatment.

摘要

背景

随着感染和其他严重并发症风险的增加，糖尿病患者伤口愈合受损的潜在分子机制值得关注。冷休克蛋白（CSPs），包括 CIRP 和 RBM3，在皮肤中高度表达；然而，目前尚不清楚 CSP 是否参与糖尿病皮肤的伤口愈合受损。

目的

本研究旨在探讨 RBM3 对糖尿病皮肤伤口愈合的影响。

方法

体外实验中，采用 Western blot 检测不同浓度葡萄糖处理的 HaCaT 细胞中蛋白水平。采用慢病毒颗粒过表达 HaCaT 细胞中的 RBM3。通过 Cell-Counting Kit-8 检测和集落形成实验分析细胞活力。通过划痕愈合实验评估不同浓度葡萄糖作用下 HaCaT 细胞的迁移。体内实验中，通过腹腔注射链脲佐菌素建立糖尿病小鼠模型。4 周后，用戊巴比妥钠腹腔注射麻醉小鼠，用于皮肤组织采集或伤口愈合实验。采用 CRISPR-Cas9 技术去除外显子 2-6 构建 RBM3 敲除小鼠，然后在有无糖尿病应激的情况下用于皮肤伤口愈合实验。

结果

在这项研究中，糖尿病标本皮肤中 RBM3 的表达发生改变，而不是 CIRP，并且 RBM3 的过表达在高葡萄糖条件下加速了 HaCaT 细胞的活力和增殖。在糖尿病条件下，RBM3 缺失导致 RBM3 敲除小鼠的伤口愈合延迟。此外，RBM3 增强了 ERK1/2 信号通路，其抑制剂 FR180204 阻断了 RBM3 过表达对糖尿病皮肤伤口愈合的有益作用。