Department of Immunology and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeollabuk-do, 54907, Republic of Korea.
Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeollabuk-do, 54538, Republic of Korea.
Sci Rep. 2018 Mar 20;8(1):4908. doi: 10.1038/s41598-018-23240-6.
C1q is known to perform several functions in addition to the role it plays in complement activation. C1q contains a collagen-like portion and DDR1 (discoidin domain receptor 1) is a well-known collagen receptor. Accordingly, we hypothesized C1q might be a novel ligand of DDR1. This study shows for the first time C1q directly induces the activation and upregulation of DDR1, and that this leads to enhanced migration and invasion of HepG2 cells. In addition, C1q was found to induce the activations of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signaling, and to increase the expressions of matrix metalloproteinases (MMP2 and 9). Our results reveal a relationship between C1q and DDR1 and suggest C1q-induced DDR1 activation signaling may be involved in the progression of hepatocellular carcinoma.
C1q 除了在补体激活中发挥作用外，还具有多种功能。C1q 含有胶原样部分，DDR1（盘状结构域受体 1）是一种众所周知的胶原受体。因此，我们假设 C1q 可能是 DDR1 的一种新型配体。本研究首次表明 C1q 可直接诱导 DDR1 的激活和上调，从而增强 HepG2 细胞的迁移和侵袭。此外，还发现 C1q 可诱导丝裂原活化蛋白激酶（MAPK）和磷酸肌醇 3-激酶（PI3K）/Akt 信号通路的激活，并增加基质金属蛋白酶（MMP2 和 9）的表达。我们的结果揭示了 C1q 与 DDR1 之间的关系，并表明 C1q 诱导的 DDR1 激活信号可能参与了肝细胞癌的进展。
