Role of renal tubular programed cell death in diabetic kidney disease

Abstract

The pathogenic mechanism of diabetic kidney disease (DKD) is involved in various functions; however, its inadequate characterisation limits the availability of effective treatments. Tubular damage is closely correlated with renal function and is thought to be the main contributor to the injury observed in early DKD. Programed cell death (PCD) occurs during the biological development of the living body. Accumulating evidence has clarified the fundamental role of abnormalities in tubular PCD during DKD pathogenesis. Among PCD types, classical apoptosis, autophagic cell death, and pyroptosis are the most studied and will be the focus of this review. Our review aims to elucidate the current knowledge of the mechanism of DKD and the potential therapeutic potential of drugs targeting tubular PCD pathways in DKD.

Renalase regulates renal tubular injury in diabetic nephropathy via the p38MAPK signaling pathway

“…The key component in the progression of DKD or main pathological feature of almost all CKD is progressive fibrosis, 5,6 and the occurrence of renal fibrosis depends on the balance between fibroblast survival and extracellular matrix generation and degradation 8 . Recent studies have shown that renal tubular epithelial cells play a decisive role in the occurrence and development of renal fibrosis 8 .…”

“…Varying degrees of renal tubular damage reportedly occur in the early stages of DN prior to glomeruli damage 4 . Damaged renal tubules mediate functional and morphological changes in its epithelial cells via various pathways and are a key component in the progression of DKD, which forms the pathological basis of tubulointerstitial fibrosis 5,6 . Therefore, it is of great clinical significance to explore the mechanism of renal tubular injury and identify early interventional targets for improving the long‐term prognosis of DN.…”

EHHADH Deficiency Regulates Pexophagy and Accelerates Tubulointerstitial Injury in Diabetic Kidney Disease

“…Tubular injury is a key factor in the development and progression of DN 31 . Abnormal lipid metabolism and oxidative stress are one of the main causes of tubular injury mediated in high glucose condition 32,33,34 .…”

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

“…According to recent research, the renal tubules and interstitium also play a very important role in the pathogenesis of DKD, and renal tubular injury occurs in the early stages of DKD and promotes the progression of renal disease. 102 Renal tubular structural changes during the development of DKD mainly include tubular cell proliferation and hypertrophy, tubular atrophy, tubular basement membrane thickening, and EMT, leading to interstitial fibrosis. 103 In particular, EMT is the process by which epithelial cells become mesenchymal cells characterised by the absence of epithelial cell markers and the upregulation of the expression of mesenchymal cell markers.…”