The collagen structure of C1q induces wound healing by engaging discoidin domain receptor 2.

The collagen structure of C1q induces wound healing by engaging discoidin domain receptor 2.
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DOI:
10.1186/s10020-021-00388-y
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发表时间:
2021-10-03
期刊:
Molecular medicine (Cambridge, Mass.)
影响因子:
--
通讯作者:
Shin JS
Shin JS
中科院分区:
其他
文献类型:
--
作者:
Hayuningtyas RA;Han M;Choi S;Kwak MS;Park IH;Lee JH;Choi JE;Kim DK;Son M;Shin JS

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据报道,C1q 在免疫和非免疫细胞中揭示了补体独立的作用。 C1q 与其特定受体结合,调节依赖于环境和细胞类型的不同功能。盘状蛋白结构域受体 2 (DDR2) 被胶原蛋白激活,并通过控制基质金属蛋白酶 (MMP) 的表达来促进伤口愈合。由于 C1q 表现出胶原蛋白样结构,我们假设 C1q 可能与 DDR2 结合来调节伤口愈合和细胞外基质 (ECM) 重塑。利用基于细胞的测定、邻近连接测定、ELISA 和表面等离子体分析来研究 DDR2 和 C1q 结合。我们还使用人类纤维肉瘤细胞系 HT1080 研究了 C1q 介导的体外伤口愈合能力。 C1q 诱导 DDR2、p38 激酶和 ERK1/2 的磷酸化。 C1q 和 DDR2 结合可改善细胞迁移并诱导 MMP2 和 MMP9 表达。 DDR2 特异性 shRNA 减少了 C1q 介导的伤口愈合细胞迁移。 C1q 是一种新的 DDR2 配体,可促进伤口愈合。这些发现对伤口愈合相关疾病具有治疗意义。
C1q has been reported to reveal complement-independent roles in immune and non-immune cells. C1q binds to its specific receptors to regulate distinct functions that rely on the environment and cell types. Discoidin domain receptor 2 (DDR2) is activated by collagen and functions in wound healing by controlling matrix metalloproteinase (MMP) expression. Since C1q exhibits a collagen-like structure, we hypothesized that C1q might engage DDR2 to regulate wound healing and extracellular matrix (ECM) remodeling. Cell-based assay, proximity ligation assay, ELISA, and surface plasmon analysis were utilized to investigate DDR2 and C1q binding. We also investigate the C1q-mediated in vitro wound healing ability using the human fibrosarcoma cell line, HT1080. C1q induced the phosphorylation of DDR2, p38 kinase, and ERK1/2. C1q and DDR2 binding improved cell migration and induced MMP2 and MMP9 expression. DDR2-specific shRNA reduced C1q-mediated cell migration for wound healing. C1q is a new DDR2 ligand that promotes wound healing. These findings have therapeutic implications in wound healing-related diseases.
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