Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR

被引：27

作者：

Gregorini, Marilena ^{[1
,2
]}

Corradetti, Valeria ^{[1
,2
]}

Rocca, Chiara ^{[1
,2
]}

Pattonieri, Eleonora Francesca ^{[1
,2
]}

Valsania, Teresa ^{[1
,2
]}

Milanesi, Samantha ^{[1
,2
]}

Serpieri, Nicoletta ^{[1
,2
]}

Bedino, Giulia ^{[1
,2
]}

Esposito, Pasquale ^{[1
,2
]}

Libetta, Carmelo ^{[1
,2
]}

Avanzini, Maria Antonietta ^{[3
]}

Mantelli, Melissa ^{[3
]}

Ingo, Daniela ^{[3
]}

Peressini, Sabrina ^{[4
]}

Albertini, Riccardo ^{[4
]}

Dal Canton, Antonio ^{[1
,2
]}

Rampino, Teresa ^{[1
,2
]}

机构：

[1] Fdn IRCCS Policlin San Matteo, Nephrol Unit, Dialysis, Transplantat, Pavia, Italy

[2] Univ Pavia, Via Palestro 3, I-27100 Pavia, Italy

[3] Fdn IRCCS Policlin S Matteo, Lab Transplant Immunol Cell Factory, Pavia, Italy

[4] Fdn IRCCS Policlin San Matteo, Clin Chem Lab, Pavia, Italy

来源：

PLOS ONE | 2016年 / 11卷 / 02期

关键词：

EXPERIMENTAL KIDNEY-TRANSPLANTATION; STEM-CELLS; MESSENGER-RNA; TUBULOINTERSTITIAL FIBROSIS; THERAPEUTIC APPLICATIONS; GLOMERULAR HEMODYNAMICS; INFLAMMATORY RESPONSE; INTERSTITIAL FIBROSIS; NEPHROPATHY; RECEPTOR;

D O I：

10.1371/journal.pone.0148542

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 TGF beta, 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 TGF beta 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.

引用

页数：19

共 63 条

[1] HADHB, HuR, and CP1 bind to the distal 3′-untranslated region of human renin mRNA and differentially modulate renin expression [J].