The effects of relaxin and estrogen deficiency on collagen deposition and hypertrophy of nonreproductive organs

被引:45
作者
Lekgabe, Edna D.
Royce, Simon G.
Hewitson, Tim D.
Tang, Mimi L. K.
Zhao, Chongxin
Moore, Xiao Lei
Tregear, Geoffrey W.
Bathgate, Ross A. D.
Du, Xiao-Jun
Samuel, Chrishan S.
机构
[1] Univ Melbourne, Howard Florey Inst, Parkville, Vic 3010, Australia
[2] Baker Heart Res Inst, Melbourne, Vic 8008, Australia
[3] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dept Immunol, Parkville, Vic 3052, Australia
[4] Royal Melbourne Hosp, Dept Nephrol, Parkville, Vic 3050, Australia
关键词
D O I
10.1210/en.2006-0533
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In this study, we determined the effects of relaxin and estrogen deficiency and estrogen replacement therapy (ERT) on the cardiac, renal, and pulmonary phenotypes of female relaxin gene knockout (Rln1-/-) and age-matched wild-type (Rln1+/+) mice. One-month-old Rln1+/+ and Rln1 -/- mice were bilaterally ovariectomized or sham-operated and aged until 9 or 12 months. A subgroup of ovariectomized mice received ERT from 9 to 12 months of age. At the appropriate time points, heart, kidney, and lung tissues from these mice were collected and analyzed for changes in organ fibrosis, hypertrophy, and airway thickening. Neither ovariectomy nor ERT had any effect on cardiac or renal collagen concentration in all groups studied. In contrast, total lung collagen concentration and airway subepithelial collagen deposition were significantly increased in ovariectomized Rln1+/+ mice (P < 0.05 vs. sham) and to a greater extent in ovariectomized Rln1+/+ mice (P < 0.01 vs. sham). Ovariectomy of Rln1-/- mice also led to a significant increase in airway smooth muscle (SM) ( lung) thickening, which was further exaggerated in Rln1-/- mice. Cardiac hypertrophy, evidenced by increased heart weight and expression of hypertrophy-related genes ( all P < 0.05 vs. sham) was only observed in Rln1 -/- mice. These findings demonstrated an increased pathology in mice that were deficient of both relaxin and estrogen. ERT significantly decreased airway fibrosis, airway SM thickening, and cardiac hypertrophy when administered to ovariectomized Rln1-/- mice ( all P < 0.05 vs. ovariectomy alone). These findings suggest that relaxin and estrogen appear to play protective roles against airway fibrosis, airway SM thickening, and cardiac hypertrophy in female mice.
引用
收藏
页码:5575 / 5583
页数:9
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