C1q mediated hepatic stellate cell activation associated with CTGF elevation and is a prognostic factor for survival in rat and human chronic liver diseases.

C1q has been determined to have multiple functions including cell migration. Current evidences shows that C1q is a ligand for Frizzled receptors (FZDs), FZD-induced YAP/TAZ activation mediated CTGF production as an alternative Wnt signaling pathway, and YAP signaling pathway is involved in HSC activation. However, no study exists in which C1q directly activate HSCs, thus, we investigate C1q's role in liver fibrosis using LX2 cells, cirrhotic rats and 91 chronic liver disease patients. C1q activated LX2 consequent up-regulated expression of CTGF and TIMP1, as well as FZD2, TAZ, and Cyr61 genes as alternative Wnt signaling pathway. In cirrhotic rats, liver C1q levels were significantly correlated with Azan positive area and CTGF, TIMP1, HAS and CD44 genes. Liver C1q, CTGF and TIMP1 levels were significantly increased in deceased group. Human serum C1q levels were significantly increased in liver cirrhosis compared to chronic hepatitis and correlated with ELF and CTGF levels. In average 66 months observation period, serum C1q levels were significantly increased in deceased patients. Serum C1q<11 mg/dL had significantly longer rates of survival compared to patients with serum C1q≥11 mg/dL. In conclusion, C1q involved in liver fibrosis through HSC activation and may be a prognostic factor for survival in chronic liver disease.