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Mannose receptor 2 attenuates renal fibrosis
Jesús M López-Guisa1, Xiaohe Cai, Sarah J Collins
1Seattle Children's Research Institute and Department of Pediatrics, University of Washington, Seattle, WA 98101-1309, USA.
Journal of the American Society of Nephrology : JASN
|November 19, 2011
Summary
Mannose receptor 2 (Mrc2) deficiency exacerbates kidney fibrosis and damage by impairing collagen turnover. Mrc2-expressing cells in the kidney interstitium protect against fibrosis, likely via a lysosomal collagen degradation pathway.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Mannose receptor 2 (Mrc2) internalizes collagen, suggesting a role in renal fibrosis.
- Mrc2 expression is low in normal kidneys but increases in myofibroblasts and macrophages post-injury.
Purpose of the Study:
- To investigate the role of Mrc2 in modulating renal fibrosis and collagen turnover.
- To determine the mechanism by which Mrc2 influences renal fibrotic disease progression.
Main Methods:
- Utilized Mrc2-deficient mice and unilateral ureteral obstruction (UUO) model.
- Analyzed renal fibrosis, parenchymal damage, collagen levels, and procollagen mRNA.
- Investigated Mrc2 association with urokinase receptor and cathepsin activity.
Main Results:
- Mrc2 deficiency significantly worsened renal fibrosis and damage after UUO.
- Mrc2-deficient mice with hereditary nephritis showed increased collagen, BUN, and proteinuria.
- Reduced collagen turnover, not urokinase activity, explained the exacerbated fibrosis.
- Cathepsin inhibition worsened fibrosis, implicating Mrc2 in collagen degradation.
Conclusions:
- Mrc2 plays a critical fibrosis-attenuating role in renal interstitial cells.
- A lysosomal collagen turnover pathway involving Mrc2 is suggested.
- Mrc2 is a potential therapeutic target for mitigating kidney fibrosis.
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