| First Author | Samuel CS | Year | 2009 |
| Journal | Endocrinology | Volume | 150 |
| Issue | 3 | Pages | 1495-502 |
| PubMed ID | 18974264 | Mgi Jnum | J:158095 |
| Mgi Id | MGI:4438008 | Doi | 10.1210/en.2008-1062 |
| Citation | Samuel CS, et al. (2009) Relaxin family peptide receptor-1 protects against airway fibrosis during homeostasis but not against fibrosis associated with chronic allergic airways disease. Endocrinology 150(3):1495-502 |
| abstractText | Endogenous relaxin has recently been demonstrated to protect the airway/lung against age-related fibrosis and against inflammation-associated airway fibrosis in animal models of allergic airways disease (AAD). In the current study, we examined the contribution of the primary relaxin receptor, relaxin family peptide receptor-1 (RXFP1), in mediating these effects of relaxin. Lung tissues from healthy aging RXFP1 gene-knockout (Rxfp1(-/-)) and wild-type (Rxfp1(+/+)) mice and from 8- to 10-wk-old Rxfp1(-/-) and Rxfp1(+/+) mice subjected to a mouse model of AAD were assessed for various markers of airway fibrosis and remodeling. Male and female Rxfp1(-/-) mice demonstrated an age-related progression of airway/lung fibrosis. Saline-treated Rxfp1(-/-) mice had significantly increased myofibroblast differentiation and lung collagen deposition (both P < 0.05), decreased matrix metalloproteinase (MMP)-9 expression and activity (P < 0.05), but equivalent levels of MMP-2 and tissue inhibitor of metalloproteinases (TIMPs) to that measured in saline-treated Rxfp1(+/+) mice. As expected, ovalbumin (OVA)-treated Rxfp1(+/+) mice developed markedly increased lung myofibroblast differentiation and collagen deposition (both P < 0.01 vs saline-treated Rxfp1(+/+) mice), significantly decreased lung MMP-2 and MMP-9 expression and activity and increased TIMP-1 expression (all P < 0.05 vs. respective measurements from saline-treated Rxfp1(+/+) mice). Surprisingly, however, OVA-treated Rxfp1(-/-) animals had equivalent levels of airway fibrosis and gelatinase activity but increased TIMP-1 expression (P < 0.05) compared with OVA-treated Rxfp1(+/+) mice. These combined findings demonstrate that RXFP1 is involved in mediating relaxin's effects on airway fibrosis during homeostasis but not during inflammation-induced fibrosis associated with chronic AAD. |
