Mechanisms of podocyte injury and implications for diabetic nephropathy

Abstract

Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, and diabetic nephropathy (DN). Moreover, albuminuria is an important feature of all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining the permselectivity of the glomerular filtration barrier (GFB) and injury of the podocyte, leading to foot process (FP) effacement and podocyte loss, the unifying underlying mechanism of proteinuric glomerulopathies. The metabolic insult of hyperglycemia is of paramount importance in the pathogenesis of DN, while insults leading to podocyte damage are poorly defined in other proteinuric glomerulopathies. However, shared mechanisms of podocyte damage have been identified. Herein, we will review the role of haemodynamic and oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, and both mitochondrial and autophagic dysfunction in the pathogenesis of the podocyte damage, focussing particularly on their role in the pathogenesis of DN. Gaining a better insight into the mechanisms of podocyte injury may provide novel targets for treatment. Moreover, novel strategies for boosting podocyte repair may open the way to podocyte regenerative medicine.

Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease

“…Damage to the glomerular filtration barrier (GFB), consisting of a fenestrated endothelium, the glomerular basement membrane, and a layer of specialized interdigitating epithelial cells, termed podocytes, plays a fundamental role in progressive development of proteinuria and glomerulosclerosis in DKD [ 52 ]. db / db UNx-ReninAAV mice demonstrated podocyte foot effacement, predicting disruption of the slit diaphragm connecting podocyte foot processes [ 53 ].…”

Circulating Permeability Factors in Focal Segmental Glomerulosclerosis: In Vitro Detection

“…Cytoskeletal rearrangement is facilitated by ROS, as the ROS scavenger DMTU prevented disruption of the podocytes' actin cytoskeleton in our experiments. This ROS-mediated cytoskeleton rearrangement is likely to be dependent on calcium influx and the balance of Rho-GTPases 49 .Interestingly, stimulation of cells with angiotensin II facilitates ROS formation as it activates NADPH oxidase in a protein kinase C-dependent manner 28 . Of note, podocyte injury in response to angiotensin II is in part mediated by TRPC6 28 45 .…”

Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy

“…113 Although the pathogenesis of DN is complex, QD NPs are developing into a new research field for diseases such as DN. [114][115][116] The polyethylene glycol coated QDs described by Pollinger et al 114 prolong drug release time in the circulatory system and can also be enriched in the renal mesangium for targeted therapy. In addition, to overcome the limitations of traditional immunohistochemical detection of multiple biomarkers, Liu et al 117 immunofluorescence labeling technology for the application of QD primary antibody probes.…”