Clq and immune complexes in liver cirrhosis sera.

Yoshida, Hiroshi; Sato, Mikio; Watanabe, Susumu; Nishimaki, Tomoe; Morito, Takao; Kasukawa, Reiji; Nakai, Masahiko

doi:10.1620/tjem.140.73

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…[ 1 ] Serum C1q levels increase with age from 45 to 75 years old, irrespective of sex differences in healthy individuals, [ 2 , 3 ] and increase in a variety of pathological conditions, including infectious and inflammatory diseases. [ 4 ] In liver diseases, human serum C1q levels were found to be increased in liver cirrhosis (LC), [ 5 ] chronic hepatitis (CH) caused by infection with hepatitis C virus (HCV), [ 6 ] and alcohol‐associated liver disease. [ 7 ] Furthermore, C1q‐mediated ethanol‐induced liver injury in mice [ 8 ] and hepatic insulin resistance in mice fed a high‐fat diet [ 9 ] occur through activation of the classical complement pathway.…”

Section: Introductionmentioning

confidence: 99%

Complement complex 1 subunit q‐mediated hepatic stellate cell activation with connective tissue growth factor elevation is a prognostic factor for survival in rat and human chronic liver diseases

et al. 2022

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Complement complex 1 subunit q (C1q) has multiple functions, including cell migration, in addition to its traditional complement‐activating effect. Research shows C1q is a ligand for frizzled receptors (FZDs). FZD‐induced yes‐associated protein (YAP)/transcriptional co‐activator with PDZ‐binding motif (TAZ) alternate Wnt signaling activation induces connective tissue growth factor (CTGF) production and hepatic stellate cell (HSC) activation. However, no study exists in which C1q directly induces CTGF in HSCs. Here, we investigated the role of C1q in HSC activation. Human HSCs (LX2) were incubated with C1q to assess HSC activation. C1q and fibrotic markers were assessed using immunohistochemistry, immunoblotting, and quantitative reverse‐transcription polymerase chain reaction in cirrhotic rats administered CCl4 for 21 weeks. Serum C1q, liver function, and fibrosis score were measured in 91 patients with chronic liver disease. The correlations between serum C1q and liver function, fibrosis score, and survival prognosis were examined. C1q‐activated LX2s showed morphologic changes, up‐regulation of CTGF, tissue inhibitors of metalloproteinases (TIMP‐1), and alternate Wnt signal genes FZD2, TAZ, and cysteine‐rich angiogenic inducer 61 (Cyr61). Cirrhotic rat liver C1q expression correlated with the Azan‐positive area and expression of CTGF, TIMP‐1, hyaluronan synthase (HAS)1, HAS3, and CD44. Expression of C1q protein and C1q, CTGF, and TIMP‐1 genes were higher in deceased cirrhotic rat livers compared to surviving rats. Human serum C1q levels increased in liver cirrhosis compared to chronic hepatitis and correlated with liver fibrosis and functional markers. Ten patients suffered liver‐related death over a 66‐month observation period. The C1q cut‐off value (11 mg/dl) showed patients with serum values < 11 mg/dl had longer rates of survival compared to C1q ≥ 11 mg/dl. Conclusion: C1q‐mediated HSC activation in liver fibrosis is associated with CTGF elevation. Additionally, serum C1q may be diagnostic for survival in human chronic liver diseases.

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Section: Introductionmentioning

confidence: 99%

Complement complex 1 subunit q‐mediated hepatic stellate cell activation with connective tissue growth factor elevation is a prognostic factor for survival in rat and human chronic liver diseases

et al. 2022

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“…C1q plays an important role during tumor development, and a recent study reported that C1q contributes to C-activation and independent tumor growth, and that C1q can promote cancer cell adhesion, migration and proliferation 7 . Patients with HCC, acute hepatitis, chronic aggressive hepatitis, and patients with cirrhosis have elevated serum C1q levels, and it has been reported serum C1q levels increase with the progress of liver damage 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

Complement C1q stimulates the progression of hepatocellular tumor through the activation of discoidin domain receptor 1

Lee

Poudel

et al. 2018

Sci Rep

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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.

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