Mast cell activation and degranulation promotes renal fibrosis in experimental unilateral ureteric obstruction View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-09

AUTHORS

Shaun A Summers, Poh-yi Gan, Lakshi Dewage, Frank T, Joshua D Ooi, Kim M O'Sullivan, David J Nikolic-Paterson, A Richard Kitching, Stephen R Holdsworth

ABSTRACT

Progressive renal fibrosis is the final common pathway leading to renal failure irrespective of the initiating cause. Clinical studies of renal fibrosis found that prominent mast cell accumulation correlated with worse outcomes. Mast cells are pluripotent innate immune cells that synthesize and secrete profibrotic mediators. Here we use mast cell-deficient (Kit(W-sh/W-sh)) mice to define a functional pathogenic role for these cells in the development of renal fibrosis. Intrarenal collagen deposition was significantly decreased in mast cell-deficient compared to wild-type mice 7 and 14 days after unilateral ureteric obstruction. The intrarenal expression of mRNAs for transforming growth factor-β, α-smooth muscle actin, chemokines, and renal macrophages and CD4(+) T cells were also decreased in mast cell-deficient mice. Reconstitution of the mast cell population in mast cell-deficient mice with wild-type bone marrow-derived mast cells restored the pattern and intensity of renal fibrosis to levels seen in wild-type mice following ureteric ligation. Interestingly, the mast cells were recruited, activated, and degranulated within 6 h of ureteric ligation. A mast cell stabilizer that impairs degranulation, disodium chromoglycate, significantly attenuated renal fibrosis following ureteric ligation in wild-type mice. Thus, mast cells promote renal fibrosis and their targeting may offer therapeutic potential in the treatment of renal fibrosis. More... »

PAGES

676-685

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ki.2012.211

DOI

http://dx.doi.org/10.1038/ki.2012.211

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018398847

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22673890


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