Matrix remodeling associated 7 proteins promote cutaneous wound healing through vimentin in coordinating fibroblast functions.

IF 5 3区 医学 Q2 IMMUNOLOGY
Ying Shen, Jinling Ning, Lu Zhao, Wei Liu, Ting Wang, Jie Yu, Yiqiang Wang
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引用次数: 2

Abstract

Wound healing depends largely on the remodeling of the extracellular matrix around and reorganization of tissue-resident cells. Matrix remodeling associated 7 (MXRA7) is a member of the matrix remodeling-associated gene family and is involved in matrix remodeling-associated processes, such as inflammatory neovascularization, liver injury, and autoimmune skin disease. To investigate whether and how MXRA7 participate in cutaneous wound healing, an ear-punching model was utilized in wild-type (WT) and MXRA7-deficient mice, and the dermal fibroblasts from these mice were further studied in vitro. Results showed that the MXRA7 deficiency impaired the wound healing process in mice. Quantitative PCR indicated that lack of MXRA7 impaired the expression of several extracellular matrix genes (e.g., MMP-2) and inhibited signaling pathways (e.g., STAT3) in healing ear tissues. In in vitro culture system, migration, contraction, or proliferation of fibroblasts was impaired upon MXRA7 deficiency. Pull-down and mass spectrum assay revealed that vimentin was among the proteins that bound MXRA7 proteins in cells, and further investigations indicate MXRA7 was an autocrine factor in fibroblasts that involved vimentin in certain ways, such as JNK and STAT3/STAT5 signaling pathways in our study. In conclusion, MXRA7 proteins promote wound healing through vimentin in coordinating fibroblast functions.

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基质重塑相关蛋白通过波形蛋白协调成纤维细胞功能促进皮肤创面愈合。
伤口愈合在很大程度上取决于周围细胞外基质的重塑和组织驻留细胞的重组。基质重塑相关基因7 (Matrix remodeling associated 7, MXRA7)是基质重塑相关基因家族的成员,参与基质重塑相关过程,如炎症性新生血管、肝损伤和自身免疫性皮肤病。为了研究MXRA7是否以及如何参与皮肤伤口愈合,我们建立了野生型(WT)和MXRA7缺失小鼠的击耳模型,并在体外进一步研究了这些小鼠的真皮成纤维细胞。结果表明,MXRA7缺失对小鼠创面愈合过程有影响。定量PCR结果显示,MXRA7的缺失会损害几个细胞外基质基因(如MMP-2)的表达,并抑制愈合耳组织中的信号通路(如STAT3)。在体外培养系统中,MXRA7缺乏会损害成纤维细胞的迁移、收缩或增殖。下拉和质谱分析显示,vimentin是细胞中与MXRA7蛋白结合的蛋白之一,进一步的研究表明,MXRA7是成纤维细胞中的一个自分泌因子,在我们的研究中,MXRA7以某种方式参与了vimentin,如JNK和STAT3/STAT5信号通路。综上所述,MXRA7蛋白通过vimentin协调成纤维细胞功能促进伤口愈合。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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