Relaxin family peptide receptor-1 protects against airway fibrosis during homeostasis but not against fibrosis associated with chronic allergic airways disease

Chrishan Samuel, Simon Royce, Bin Cheng, Huifang Cao, Jan Gossen, Geoffrey Tregear, Mimi Tang

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1495 - 1502
Number of pages8
JournalEndocrinology
Volume150
Issue number3
DOIs
Publication statusPublished - 2009
Externally publishedYes

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