Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction

Abstract

Ureteric obstruction is frequently encountered in primary care urology and can lead to damage to the ipsilateral kidney. Relief of all types of obstruction generally leads to the normalization of any deterioration in renal function noted at diagnosis. However, some evidence from animal models suggests that obstruction can cause progressive deleterious effects on renal function and blood pressure control, especially in the presence of preexisting pathologies such as essential hypertension. The last 10 years have seen a proliferation of studies in rodents wherein complete unilateral ureteric obstruction has been used as a model of renal fibrosis. However, the relevance of the findings to human obstructive uropathy has, in many cases, not been the primary aim. In this review, we outline the major events linking damage to the renal parenchyma and cell death to the evolution of fibrosis following obstruction. Special focus is given to the role of apoptosis as a major cause of cell death during and post-complete ureteric obstruction. Several interventions that reduce tubular apoptosis are discussed in terms of their ability to prevent subsequent progression to end-organ damage and fibrosis.

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

“…40 The involvement of tubular cell apoptosis in renal interstitial fibrosis during UUO has also been documented by previous studies. 41,42 To determine the role of autophagy in UUO-induced tubular cell apoptosis, we performed TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining (Fig. 3).…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…To a certain extent TECs can compensate for stress, as in selective albuminuria, however, if the injury gets more pronounced, the adaptive response will lead to fibrosis and progressive kidney disease (126). Processes involved in mediating the profibrotic response include TEC senescence (6,127,128), apoptosis (129,130), autophagy (131,132), and endoplasmic reticulum stress (133,134), however, many of these processes can also have beneficial effects under certain conditions (135,136). Another process leading to profibrotic activation of TECs is cell cycle arrest (137).…”

Autophagy Is a Component of Epithelial Cell Fate in Obstructive Uropathy

“…26,27 In Cre ksp ;R26R-EYFP mice, ureteral obstruction led to the gradual atrophy of tubules and decreased number of EYFP-expressing cells ( Figure 3A, upper panel). The kidneys were further examined for the expression of epithelial markers E-cadherin ( Figure 3A, lower panel) and HNF-1␤ ( Figure 3B).…”