The Role of Relaxin-2 in Tissue Remodeling of Chronic Rhinosinusitis With Nasal Polyps

Abstract

Background Relaxin is a small peptide hormone that regulates extracellular matrix remodeling and reduces fibrosis in a number of organs. Little is known about its impact on chronic rhinosinusitis with nasal polyps (CRSwNP); thus, we aimed to determine the expression of human H2 relaxin (relaxin-2) and its role in tissue remodeling in CRSwNP. Methods Patients were enrolled and divided into the following groups: CRS with NP (CRSwNP; n = 20), CRS without NP (CRSsNP; n = 20), and controls (n = 15). Tissue samples were analyzed by Masson trichrome staining for collagen, while the location and expression of relaxin-2, transforming growth factor beta 1 (TGF-β1), and phosphorylated (p) Smad2/Smad3 were analyzed by immunohistochemistry and Western blot. The expression of relaxin-2, Smad2, Smad3, and TGF-β1 mRNA was tested by quantitative polymerase chain reaction (qPCR). Ex vivo NP were treated with relaxin-2 (n = 15) or TGF-β1 (n = 15). Collagen type I (collagen I), relaxin-2, and TGF-β1 levels in the culture supernatants were examined by enzyme-linked immunosorbent assay, while pSmad2/Smad3 in culture pellets was analyzed by Western blot, and the expression of Smad2 and Smad3 mRNA was tested by qPCR. Results The collagen, relaxin-2, TGF-β1, and pSmad2/Smad3 protein expression levels were significantly decreased in the CRSwNP group compared with the CRSsNP group ( P < .05). The expression of relaxin-2, Smad2, Smad3, and TGF-β1 mRNA in the CRSsNP group was significantly higher than in the CRSwNP and control groups ( P < .05). Compared with the ex vivo controls, in CRSwNP, the levels of TGF-β1, collagen I, pSmad2/Smad3, Smad2, and Smad3 were markedly decreased after relaxin-2 treatment. However, relaxin-2, collagen I, pSmad2/Smad3, Smad2, and Smad3 were remarkably increased after TGF-β1 treatment. Conclusions The antifibrotic effects of relaxin-2 may play a role in tissue remodeling in CRSwNP, but the detailed mechanism deserves further study.