» Articles » PMID: 15917339

Rapamycin Ameliorates Proteinuria-associated Tubulointerstitial Inflammation and Fibrosis in Experimental Membranous Nephropathy

Overview
Specialty Nephrology
Date 2005 May 27
PMID 15917339
Citations 58
Authors
Affiliations
Soon will be listed here.
Abstract

Proteinuria is a risk factor for progression of chronic renal failure. A model of proteinuria-associated tubulointerstitial injury was developed and was used to examine the therapeutic effect of rapamycin. Two studies were performed. In study A, proteinuric rats were given sheep anti-Fx1A to induce experimental membranous nephropathy; control rats received normal sheep serum. Four weeks later, groups were subdivided and underwent laparotomy alone (two kidneys), nephrectomy alone (one kidney), or nephrectomy with polectomy (0.6 kidney). Renal function and morphology were evaluated 4 wk later. Whereas control rats never developed proteinuria, anti-Fx1A induced severe proteinuria. Proteinuria was unaffected by renal mass reduction. Proteinuric rats developed tubulointerstitial disease that was most severe in rats with 0.6 kidneys. Renal function (GFR) was reduced by loss of renal mass and was reduced further in proteinuric rats with 0.6 kidneys. In study B, the effect of rapamycin on the expression of candidate proinflammatory and profibrotic genes and the progression of proteinuria-associated renal disease were examined. All rats received an injection of anti-Fx1A and were nephrectomized and then divided into groups to receive rapamycin or vehicle. Gene expression, renal morphology, and GFR were evaluated after 4, 8, and 12 wk. Rapamycin reduced expression of the proinflammatory and profibrotic genes (monocyte chemotactic protein-1, vascular endothelial growth factor, PDGF, TGF-beta(1), and type 1 collagen). Tubulointerstitial inflammation and progression of interstitial fibrosis that were present in vehicle-treated rats were ameliorated by rapamycin. Rapamycin also completely inhibited compensatory renal hypertrophy. In summary, rapamycin ameliorates the tubulointerstitial disease associated with chronic proteinuria and loss of renal mass.

Citing Articles

Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy.

Gui C, Liu S, Fu Z, Li H, Zhang D, Deng Y Heliyon. 2024; 10(21):e38424.

PMID: 39524772 PMC: 11546183. DOI: 10.1016/j.heliyon.2024.e38424.


Crosstalk between the mTOR pathway and primary cilia in human diseases.

Prosseda P, Dannewitz Prosseda S, Tran M, Liton P, Sun Y Curr Top Dev Biol. 2023; 155:1-37.

PMID: 38043949 PMC: 11227733. DOI: 10.1016/bs.ctdb.2023.09.004.


Rapid diagnosis of membranous nephropathy based on serum and urine Raman spectroscopy combined with deep learning methods.

Zhang X, Song X, Li W, Chen C, Wusiman M, Zhang L Sci Rep. 2023; 13(1):3418.

PMID: 36854769 PMC: 9974944. DOI: 10.1038/s41598-022-22204-1.


Sirolimus suppresses circulating fibrocytes in idiopathic pulmonary fibrosis in a randomized controlled crossover trial.

Gomez-Manjarres D, Axell-House D, Patel D, Odackal J, Yu V, Burdick M JCI Insight. 2023; 8(8).

PMID: 36853800 PMC: 10243828. DOI: 10.1172/jci.insight.166901.


Combination therapy with DHA and BMSCs suppressed podocyte injury and attenuated renal fibrosis by modulating the TGF-1/Smad pathway in MN mice.

Li Y, Chen S, Tan J, Zhou Y, Ren M, Zhang Q Ren Fail. 2023; 45(1):2120821.

PMID: 36648018 PMC: 9848254. DOI: 10.1080/0886022X.2022.2120821.