Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease

Ishanee Mookerjee, Natasha Solly, Simon Royce, Geoffrey Tregear, Chrishan Samuel, Mimi Tang

Research output: Contribution to journalArticleResearchpeer-review

48 Citations (Scopus)

Abstract

We examined the relationship among relaxin (a peptide hormone that stimulates collagen degradation), airway fibrosis, other changes of airway remodeling, and airway hyperresponsiveness (AHR) in an animal model of allergic airway disease. Eight- to 10-wk-old relaxin gene-knockout (RLX(-/-)) and wild-type (RLX(+/+)) mice were sensitized with ovalbumin (OVA) or saline ip at d 0 and 14 and challenged three times per week for 6 wk with nebulized 2.5 OVA or saline. Saline-treated control RLX(+/+) and RLX(-/-) mice had equivalent collagen expression and baseline airway responses. OVA-treated RLX(-/-) mice developed airway inflammation equivalent to that in OVA-treated RLX(+/+) mice. However, OVA-treated RLX(-/-) mice had markedly increased lung collagen deposition as compared with OVA-treated RLX(+/+) and saline-treated mice (all P <0.05). Collagen was predominantly deposited in the subepithelial basement membrane region and submucosal regions in both OVA-treated RLX(+/+) and RLX(-/-) mice. The increased collagen measured in OVA-treated RLX(-/-) mice was associated with reduced matrix metalloproteinase (MMP)-9 (P <0.02) expression and failure to up-regulate matrix metalloproteinase-2 expression, compared with levels in OVA-treated RLX(+/+) mice. Goblet cell numbers were equivalent in OVA-treated RLX(-/-) and RLX(+/+) mice and increased, compared with saline-treated animals. Both OVA-treated RLX(+/+) and RLX(-/-) mice developed similar degrees of AHR after OVA treatment. These findings demonstrate a critical role for relaxin in the inhibition of lung collagen deposition during an allergic inflammatory response. Increased deposition of collagen per se did not influence airway epithelial structure or AHR.
Original languageEnglish
Pages (from-to)754 - 761
Number of pages8
JournalEndocrinology
Volume147
Issue number2
DOIs
Publication statusPublished - 2006
Externally publishedYes

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