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Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR.
- Source :
-
PloS one [PLoS One] 2016 Feb 11; Vol. 11 (2), pp. e0148542. Date of Electronic Publication: 2016 Feb 11 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- We studied Mesenchymal Stromal Cells (MSC) effects in experimental Unilateral Ureteral Obstruction (UUO), a fibrogenic renal disease. Rats were divided in 5 groups: sham, UUO, MSC treated-UUO, ACEi treated-UUO, MSC+ACEi treated- UUO. Data were collected at 1, 7, 21 days. UUO induced monocyte renal infiltration, tubular cell apoptosis, tubular atrophy, interstitial fibrosis and overexpression of TGFβ, Renin mRNA (RENmRNA), increase of Renin, Angiotensin II (AII) and aldosterone serum levels. Both lisinopril (ACEi) and MSC treatment prevented monocyte infiltration, reduced tubular cell apoptosis, renal fibrosis and TGFβ expression. Combined therapy provided a further suppression of monocyte infiltration and tubular injury. Lisinopril alone caused a rebound activation of Renin-Angiotensin System (RAS), while MSC suppressed RENmRNA and Renin synthesis and induced a decrease of AII and aldosterone serum levels. Furthermore, in in-vitro and in-vivo experiments, MSC inhibit Human antigen R (HuR) trascription, an enhancer of RENmRNA stability by IL10 release. In conclusion, we demonstrate that in UUO MSC prevent fibrosis, by decreasing HuR-dependent RENmRNA stability. Our findings give a clue to understand the molecular mechanism through which MSC may prevent fibrosis in a wide and heterogeneous number of diseases that share RAS activation as common upstream pathogenic mechanism.
- Subjects :
- Aldosterone metabolism
Angiotensin II metabolism
Animals
Animals, Genetically Modified
Apoptosis
Cell Differentiation
Cell Line
Disease Models, Animal
Green Fluorescent Proteins metabolism
Humans
Immunophenotyping
Interleukin-10 metabolism
Kidney Tubules pathology
Male
Rats
Rats, Sprague-Dawley
Renin biosynthesis
Transforming Growth Factor beta metabolism
Ureteral Obstruction therapy
ELAV-Like Protein 1 physiology
Fibrosis physiopathology
Kidney physiopathology
Mesenchymal Stem Cells cytology
Renin-Angiotensin System
Ureteral Obstruction physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26866372
- Full Text :
- https://doi.org/10.1371/journal.pone.0148542