Mast cells decrease renal fibrosis in unilateral ureteral obstruction.
Mast cells regulate both inflammatory responses and tissue repair in human diseases but there are conflicting reports on the role of these cells in the pathogenesis of various kidney diseases. Here we measured mast cell function in unilateral ureteral obstruction, a well-characterized model of renal fibrosis, using Kit(W)/Kit(W-v) mice genetically deficient in mast cells, wild-type mice, and deficient mice reconstituted by adoptive transfer with mast cells from the wild-type animals. Mast cell-deficient mice had higher levels of renal tubular damage, more stromal fibrosis, higher numbers of infiltrating ERHR3-positive macrophages and CD3-positive T cells, and higher tissue levels of profibrotic transforming growth factor-beta1 than wild-type mice or mice reconstituted by adoptive transfer of mast cells 3 weeks after ureteral obstruction. Similarly, while wild-type and adoptively transferred mice had increased alpha-smooth muscle actin and decreased E-cadherin expression, which are indicators of epithelial-mesenchymal transition, the obstructed kidneys of the mast cell-deficient mice had significant attenuation of those indicators. Thus, our study suggests that mast cells protect the kidney against fibrosis by modulation of inflammatory cell infiltration and by transforming growth factor-beta1-driven epithelial-to-mesenchymal transitions.
Kim
Duk Hoon
DH
Renal Regeneration Laboratory and Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
Moon
Sang-Ok
SO
Jung
Yu Jin
YJ
Lee
Ae Sin
AS
Kang
Kyung Pyo
KP
Lee
Tae Hwan
TH
Lee
Sik
S
Chai
Ok Hee
OH
Song
Chang Ho
CH
Jang
Kyu Yun
KY
Sung
Mi Jeong
MJ
Zhang
Xin
X
Park
Sung Kwang
SK
Kim
Won
W
D000818:Animals; D004847:Epithelial Cells / Q000166:cytology; D005355:Fibrosis / Q000209:etiology*; D007674:Kidney Diseases / Q000473:pathology*; D008262:Macrophage Activation; D008407:Mast Cells / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains; D053773:Transforming Growth Factor beta1; D014517:Ureteral Obstruction / Q000473:pathology*
D053773:Transforming Growth Factor beta1