Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy

Abstract

Renal fibrosis is the hallmark of progressive renal disease of virtually any etiology. The model of unilateral ureteral obstruction (UUO) in the rodent generates progressive renal fibrosis. Surgically created UUO can be experimentally manipulated with respect to timing, severity, and duration, while reversal of the obstruction permits the study of recovery. The use of genetically engineered mice has greatly expanded the utility of the model in studying molecular mechanisms underlying the renal response to UUO. Ureteral obstruction results in marked renal hemodynamic and metabolic changes, followed by tubular injury and cell death by apoptosis or necrosis, with interstitial macrophage infiltration. Proliferation of interstitial fibroblasts with myofibroblast transformation leads to excess deposition of the extracellular matrix and renal fibrosis. Phenotypic transition of resident renal tubular cells, endothelial cells, and pericytes has also been implicated in this process. Technical aspects of the UUO model are discussed in this review, including the importance of rodent species or strain, the age of the animal, surgical procedures, and histological methods. The UUO model is likely to reveal useful biomarkers of progression of renal disease, as well as new therapies, which are desperately needed to allow intervention before the establishment of irreversible renal injury.

Basigin/CD147 Promotes Renal Fibrosis after Unilateral Ureteral Obstruction

“…45 TGF-␤ is produced by many types of cells in the UUO model, and macrophage is one of the major sources. 42,45 We found that TGF-␤ was equally up-regulated in both genotypes until 7 days after UUO surgery ( Figure 2D). Then TGF-␤ expression in Bsg ϩ/ϩ exceeded that in Bsg Ϫ/Ϫ mice at day 14 ( Figure 2D).…”

“…42,43 Both Bsg ϩ/ϩ and Bsg Ϫ/Ϫ mice exhibited only slight macrophage infiltration at day 3 (Figure 2A). Macrophage infiltration into the interstitium became prominent at day 7, and increased more at day 14 ( Figure 2, A and B).…”

Acetyl‐11‐keto‐β‐boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF‐β/Smad signalling pathway

“…Unilateral ureteral obstruction is a classic model for renal interstitial fibrosis research,17 renal hemodynamic and metabolic markedly changes after ureteral obstruction, and these sustained changes lead to the transformation of interstitial fibroblasts and excess deposition of EMC. In our results, significant disruption of the renal function indices was observed in UUO kidneys by detecting the kidney/body weight, BUN and Scr values.…”

Discoidin Domain Receptor 1 Is a Major Mediator of Inflammation and Fibrosis in Obstructive Nephropathy

“…It is well established that the natural history of UUO is characterized by the early onset of renal interstitial inflammation as a consequence of the production of proinflammatory cytokines, such as MCP-1, by resident in- terstitial and epithelial cells. 27,28 Specifically, infiltration by activated macrophages plays a central role in the inflammatory response to UUO and in the progression of the subsequent renal disease. 29 -32 When compared with the renal localization of DDR1 expression in murine hypertension-induced renal disease and in Col4A3-deficient mice, our present results, consistent with recent observations of DDR1 ϩ macrophages in atherosclerosis, suggest that DDR1 appears to be induced in cell types that are predominantly activated by the specific disease process and involved in the response to the local injury.…”