Kisspeptin-10 increases collagen content in the myocardium by focal adhesion kinase activity

The aim of the study was to evaluate the role of kisspeptin-10 (KiSS-10) in the regulation of collagen content in cardiac fibroblasts. An attempt was also made to describe the mechanism of the effect of KiSS-10 on collagen metabolism. The studies indicate that kisspeptin-10 significantly increases the content of intracellular collagen in the myocardium. KiSS-10 also elevates the level of phosphorylated focal adhesion kinase (FAK) in human cardiac fibroblasts. The inhibition of FAK negates the stimulatory effect of KiSS-10 on collagen deposition in vitro. These changes correlate with an increase in the level of propeptides of procollagen type I (PICP) and III (PIIICP) in fibroblast culture medium and mouse PIIICP in serum. Moreover, this hormone inhibits the release of metalloproteinases (MMP-1,-2,-9) and elevates the secretion of their tissue inhibitors (TIMP-1,-2,-4). KiSS-10 also enhances the expression of α1 chains of procollagen type I and III in vitro. Thus, KiSS-10 is involved in the regulation of collagen metabolism and cardiac fibrosis. Augmentation of collagen deposition by KiSS-10 is dependent on the protein synthesis elevation, inhibition of MMPs activity (increase of TIMPs release) or decrease of MMPs concentration. The profibrotic activity of KiSS-10 is mediated by FAK and is not dependent on TGF-β1.