Pathophysiology of diabetic kidney disease and autophagy: A review

Abstract

Diabetic kidney disease (DKD) is one of the main complications of diabetic microangiopathy. The pathogenesis of DKD is very complex, including autophagy, inflammation, oxidative stress. Although a series of treatment intervention have achieved certain results in the treatment of diabetic nephropathy, still cannot reverse the kidney injury of diabetic nephropathy. The kidney is one of the most important organs of energy metabolism. Renal function is highly dependent on phagocytosis of mitochondria, and aberrant or defective autophagic mechanisms are central to the pathology of many renal diseases. Under high glucose conditions, mitochondrial fragments accumulate in the kidney, suggesting that mitochondrial clearance mechanisms may be attenuated with changes in mitochondrial transformation mechanisms. However, the exact mechanism of mitophagy regulation in DKD has not been elucidated. Recent advances in autophagy have renewed interest in these signaling pathways and molecules in the pathogenesis of DKD. Investigating autophagy and its associated signaling molecules may provide potential unique targets for therapeutic intervention in DKD.

Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease

“…This regulation can lead to a downregulation of NOS, a key factor in maintaining vascular endothelial relaxation, and an upregulation of endothelin 1, which contributes to vascular endothelial contraction. Moreover, PKC activation can also enhance the expression of collagen fibers and proinflammatory factors, ultimately expediting renal fibrosis [128,129]. This process is facilitated by transcription factor β, plasminogen activator inhibitor 1 (PAI-1), and NF-κB.…”

Lipid metabolism disorder in diabetic kidney disease

“…Autophagy is an intracellular pathway that maintains cellular homeostasis by degrading cytoplasmic components via autolysosome formation of autolysosomes (135). Studies have shown that the development of DKD is associated with defective renal autophagy (119,(136)(137)(138)(139)(140). In DKD, the microtubuleassociated protein 1A/1b-light chain 3 (LC3-II) is dependent on phagocytosis of endoplasmic reticulum membranes to form lipid autophagosomes, which with their cargoes, mainly composed of ChE and TG, fuse with lysosomes to form autophagic lysosomes, in which the cargo is degraded to produce FAs, a process known as lipophagy (141-147).…”