RBM3通过ERK1/2信号促进糖尿病皮肤伤口愈合

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-11-01 DOI:10.2174/0118761429260980231005105929

Jianguo Feng, Menghong Long, Xin Zhao, Pijun Yan, Yunxiao Lin, Maohua Wang, Wenhua Huang

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引用次数: 0

摘要

背景:随着感染和其他严重并发症的风险增加，糖尿病创面愈合障碍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损伤。目的:探讨RBM3对糖尿病患者皮肤创面愈合的影响。方法:体外实验采用western blot法检测不同浓度葡萄糖处理HaCaT细胞的蛋白水平。利用慢病毒颗粒在HaCaT细胞中过表达RBM3。采用细胞计数试剂盒-8法和菌落形成法分析细胞活力。通过伤口愈合实验，观察不同浓度葡萄糖对HaCaT细胞迁移的影响。体内实验，通过腹腔注射链脲佐菌素建立小鼠糖尿病模型。4周后，腹腔注射戊巴比妥钠麻醉小鼠进行皮肤组织采集或创面愈合实验。利用聚集规律间隔短回文重复(CRISPR)-Cas9技术，通过去除2-6外显子建立RBM3敲除小鼠，然后用于有或无糖尿病应激的皮肤伤口愈合实验。结果:在本研究中，糖尿病标本皮肤中RBM3的表达发生了改变，而不是CIRP的表达，高糖条件下RBM3的过表达加速了HaCaT细胞的活力和增殖。RBM3缺失导致糖尿病患者RBM3基因敲除后伤口愈合延迟。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创面愈合的有益作用。结论:RBM3激活ERK1/2信号促进糖尿病皮肤创面愈合，为糖尿病的治疗提供了新的治疗靶点。

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

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. Objective: 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.

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.