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

Cite this

Mookerjee, Ishanee ; Solly, Natasha ; Royce, Simon ; Tregear, Geoffrey ; Samuel, Chrishan ; Tang, Mimi. / Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease. In: Endocrinology. 2006 ; Vol. 147, No. 2. pp. 754 - 761.
@article{3b27d21e00a1462da83c646043eeeba6,
title = "Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease",
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.",
author = "Ishanee Mookerjee and Natasha Solly and Simon Royce and Geoffrey Tregear and Chrishan Samuel and Mimi Tang",
year = "2006",
doi = "10.1210/en.2005-1006",
language = "English",
volume = "147",
pages = "754 -- 761",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "Endocrine Society",
number = "2",

}

Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease. / Mookerjee, Ishanee; Solly, Natasha; Royce, Simon; Tregear, Geoffrey; Samuel, Chrishan; Tang, Mimi.

In: Endocrinology, Vol. 147, No. 2, 2006, p. 754 - 761.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease

AU - Mookerjee, Ishanee

AU - Solly, Natasha

AU - Royce, Simon

AU - Tregear, Geoffrey

AU - Samuel, Chrishan

AU - Tang, Mimi

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16254028

U2 - 10.1210/en.2005-1006

DO - 10.1210/en.2005-1006

M3 - Article

VL - 147

SP - 754

EP - 761

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 2

ER -