Complement C1r serine protease contributes to kidney fibrosis.

Area of Science:

• Nephrology
• Immunology
• Molecular Biology

Background:

• Complement activation is linked to kidney fibrosis.
• Cellular mechanisms driving this transition remain unclear.
• C1r protease initiates complement activation.

Purpose of the Study:

• Investigate the role of C1 complex protease C1r in kidney fibrosis.
• Determine if C1r contributes to tubulointerstitial fibrosis.
• Elucidate the cellular mechanisms of C1r-mediated fibrosis.

Main Methods:

• Utilized C1r-null mice and folic acid (FA) administration.
• Performed immunohistochemistry, in situ hybridization, and differential gene expression analysis.
• Conducted in vitro experiments with renal epithelial cells.

Main Results:

• FA-induced C1r upregulation in kidney tubular epithelial cells.
• C1r-null mice showed reduced acute tubular injury, inflammation, and fibrosis.
• C1r deletion decreased C1s expression, C3 fragment formation, and fibrotic gene expression.
• Interferon-γ induced C1r and C1s expression in vitro.

Conclusions:

• Increased C1 complex protease expression is associated with kidney inflammation and C3 formation.
• C1r plays a critical role in mediating FA-induced tubulointerstitial fibrosis.
• Targeting C1r may offer a therapeutic strategy for kidney fibrosis.