Title:RBM3 Accelerates Wound Healing of Skin in Diabetes through ERK1/2
Signaling
Volume: 17
Author(s): Jianguo Feng*, Menghong Long, Xin Zhao, Pijun Yan, Yunxiao Lin, Maohua Wang*Wenhua Huang*
Affiliation:
- 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
- Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou,
China
- 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
- Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou,
China
Keywords:
Cold shock proteins, Cell migration, Diabetes, ERK1/2, RBM3, Wound healing.
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.