Des-Arg super(10)-kallidin Engagement of the B1 Receptor Stimulates Type I Collagen Synthesis via Stabilization of Connective Tissue Growth Factor mRNA

• Published in: The Journal of biological chemistry Vol. 275; no. 17; pp. 12475 - 12480
• Main Authors: Ricupero, DA, Romero, J R, Rishikof, D C, Goldstein, R H
• Format: Journal Article
• Language: English
• Published: 28.04.2000
• Subjects: connective tissue growth factor; fibrogenesis; kallidin; kinin B1 receptors
• ISSN: 0021-9258
• DOI: 10.1074/jbc.275.17.12475

Expression of the kinin B1 receptor is up-regulated in chronic inflammatory and fibrotic disorders; however, little is known about its role in fibrogenesis. We examined human embryonic lung fibroblasts that constitutively express the B1 receptor and report that engagement of the B1 receptor by des-Arg super(10)-kallidin stabilized connective tissue growth factor (CTGF) mRNA, stimulated an increase in alpha 1(I) collagen mRNA, and stimulated type I collagen production. These events were not observed in B2 receptor-activated fibroblasts. In addition, B1 receptor activation by des-Arg super(10)-kallidin induced a rise in cytosolic Ca super(2+) that is consistent with B1 receptor pharmacology. Our results show that the des-Arg super(10)-kallidin-stimulated increase in alpha 1(I) collagen mRNA was time- and dose-dependent, with a peak response observed at 20 h with 100 nM des-Arg super(10)-kallidin. The increase in CTGF mRNA was also time- and dose-dependent, with a peak response observed at 4 h with 100 nM des-Arg super(10)-kallidin. The increase in CTGF mRNA was blocked by the B1 receptor antagonist des-Arg super(10),Leu super(9)-kallidin. Inhibition of protein synthesis by cycloheximide did not block the des-Arg super(10)-kallidin-induced increase in CTGF mRNA. These results suggest that engagement of the kinin B1 receptor contributes to fibrogenesis through increased expression of CTGF.