Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments

Abstract

Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β1), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included.

Remdesivir inhibits renal fibrosis in obstructed kidneys

“…The limitation of this study is that UUO model is not suitable to study the pharmaceutical effect on renal function. UUO model is a classic model to study renal fibrosis, although we did observe a slightly increase in Scr and BUN levels in UUO mice as compared with that in sham mice (21). The renal and liver function were assessed in this study to exclude the potential toxic effect of remdesivir, and we show no effect of remdesivir on renal and liver function in this study.…”

Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model

“…Apart from TGF-β inhibitors, an anti-CTCF monoclonal antibody, the small molecule AA123 that mimics BMP-7, and Gal-3 inhibitors all performed poorly in clinical trials [30]. Unilateral ureteral obstruction (UUO) and TGF-β1induction of HK-2 cells are well-established in vivo and in vitro models [31][32][33], respectively, of human renal fibrosis that have been used extensively by researchers to better understand the pathogenesis of this devastating disease. In this study, a UUO-induced rat model of tubulointerstitial fibrosis and TGF-β1-induced HK-2 cells were used to test the therapeutic effect of BMSC-EVs and its underlying mechanisms.…”

Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model

“…Apart from TGF-β inhibitors, an anti-CTCF monoclonal antibody, the small molecule AA123 that mimics BMP-7, and Gal-3 inhibitors all performed poorly in clinical trials [30]. Unilateral ureteral obstruction (UUO) and TGF-β1-induction of HK-2 cells are well-established in vivo and in vitro models [31][32][33], respectively, of human renal fibrosis that have been used extensively by researchers to better understand the pathogenesis of this devastating disease. In this study, a UUO-induced rat model of tubulointerstitial fibrosis and TGF-β1-induced HK-2 cells were used to test the therapeutic effect of BMSC-EVs and its underlying mechanisms.…”