Abstract
Reduced Na+-K+-ATPase function is reported in various renal diseases. This implies that increase of Na+-K+-ATPase function may be a new target in treatment of renal injury. We previously reported that Na+-K+-ATPase was stabilized by DRm217, a specific antibody against DR region of Na+-K+-ATPase. In this study, we compared the protective effect of DRm217 and ouabain on kidney in a chronic kidney disease rat model and investigated the mechanism under it. We found that DRm217 improved renal function, alleviated glomerulus atrophy, inhibited renal tubular cells apoptosis, tubulointerstitial injury and renal fibrosis in 5/6 nephrectomized rats. Contrary to DRm217, ouabain worsened renal damage. Activated Na+-K+-ATPase /Src signaling pathway, increased oxidant stress and activated inflammasome were responsible for nephrectomized or ouabain-induced renal injury. DRm217 inhibited Na+-K+-ATPase /Src signaling pathway, retarded oxidant stress, suppressed inflammasome activation, and improved renal function, suggesting a novel approach to prevent renal damage.
Highlights
Chronic kidney disease (CKD) is a progressive disease which leads to gradual loss of kidney function in all age groups [1]
DRm217 significantly reduced but ouabain promoted these histological score (Figure 2C, D). This information further confirmed that DRm217 alleviated but ouabain strengthened renal injury
CKD is characterized by an irreversible deterioration of renal function, with glomerular atrophy, glomerular compensatory hypertrophy, nephric tubular degeneration, and renal fibrosis as the final common pathologic change
Summary
Chronic kidney disease (CKD) is a progressive disease which leads to gradual loss of kidney function in all age groups [1]. The precise prevalence of CKD is still not known. It is estimated that there are approximately 7% young adults and 35% elders suffer from CKD [2]. It leads to progressive renal failure and cardiovascular system diseases, including heart failure [3]. Though much have been learned about the mechanism of CKD, fewer therapeutic strategies have been shown to improve renal outcome. The development of innovative therapies to prevent renal damage in CKD is very important
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