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

Autor: Ria Aryani Hayuningtyas, Myeonggil Han, Seoyeon Choi, Man Sup Kwak, In Ho Park, Ji-Hyun Lee, Ji Eun Choi, Dae Ki Kim, Myoungsun Son, Jeon-Soo Shin
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Medicine, Vol 27, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 1076-1551
1528-3658
DOI: 10.1186/s10020-021-00388-y
Popis: Abstract Background 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. Methods 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. Results 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. Conclusions C1q is a new DDR2 ligand that promotes wound healing. These findings have therapeutic implications in wound healing-related diseases.
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