Non-genetic mechanisms of diabetic nephropathy

Han, Qiuxia; Zhu, Hanyu; Chen, Xiangmei; Liu, Zhangsuo

doi:10.1007/s11684-017-0569-9

Cited by 55 publications

(46 citation statements)

References 120 publications

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“…It has been described that podocyte number correlates with proteinuria and it is one of the best predictors of DKD . In addition to other pathogenic mechanisms as hyperglycaemia‐induced ROS generation, inflammation can contribute to podocyte loss by causing podocyte apoptosis and detachment. As podocytes are terminally differentiated cells that cannot be replaced, the remaining podocytes enlarge by cell hypertrophy and finally dedifferentiate to cell type that contribute to extracellular matrix accumulation.…”

Section: Discussionmentioning

confidence: 99%

Exploring macrophage cell therapy on Diabetic Kidney Disease

Guiteras

Solà

Flaquer

et al. 2018

J Cellular Molecular Medi

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Alternatively activated macrophages (M2) have regenerative properties and shown promise as cell therapy in chronic kidney disease. However, M2 plasticity is one of the major hurdles to overcome. Our previous studies showed that genetically modified macrophages stabilized by neutrophil gelatinase‐associated lipocalin (NGAL) were able to preserve their M2 phenotype. Nowadays, little is known about M2 macrophage effects in diabetic kidney disease (DKD). The aim of the study was to investigate the therapeutic effect of both bone marrow‐derived M2 (BM‐фM2) and ф‐NGAL macrophages in the db/db mice. Seventeen‐week‐old mice with established DKD were divided into five treatment groups with their controls: D+BM‐фM2; D+ф‐BM; D+ф‐NGAL; D+ф‐RAW; D+SHAM and non‐diabetic (ND) (db/‐ and C57bl/6J) animals. We infused 1 × 106 macrophages twice, at baseline and 2 weeks thereafter. BM‐фM2 did not show any therapeutic effect whereas ф‐NGAL significantly reduced albuminuria and renal fibrosis. The ф‐NGAL therapy increased the anti‐inflammatory IL‐10 and reduced some pro‐inflammatory cytokines, reduced the proportion of M1 glomerular macrophages and podocyte loss and was associated with a significant decrease of renal TGF‐β1. Overall, our study provides evidence that ф‐NGAL macrophage cell therapy has a therapeutic effect on DKD probably by modulation of the renal inflammatory response caused by the diabetic milieu.

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Section: Discussionmentioning

confidence: 99%

Exploring macrophage cell therapy on Diabetic Kidney Disease

Guiteras

Solà

Flaquer

et al. 2018

J Cellular Molecular Medi

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“…For example, peripheral neuropathy is actually a function of direct damage to neurons with only a small amount of neuropathy suggested due to microvascular disease (31). Similarly, in diabetic nephropathy, typified by glomerular hyper-perfusion and renal hyperfiltration-classically signs of damage to the renal microvascular apparatus-have now been recognized to be associated with cellular damage from inflammation and apoptosis (32)(33)(34). In this same way, diabetic retinopathy is now recognized to result not only in damage to micro-vessels in the retina but to cell and tissues in the retinal neuro-vascular unit (including the glial and neuronal cells as well as the microvasculature) leading to retinal dysfunction (18)(19)(20)(21)(22)29).…”

Section: Introductionmentioning

confidence: 99%

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Sinclair

Schwartz

2019

Front. Endocrinol.

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Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

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“…DN is additionally one of the leading causes of end-stage kidney disease, which only has an ~20% 5-year survival rate ( 5 ). DN has been characterized by a series of abnormal pathological alterations, including glomerular hypertrophy, mesangial proliferation, thickening of the glomerular basement membrane, and accumulation of the extracellular matrix ( 6 , 7 ). However, the dysregulated molecules and the mechanisms involved in this manifestation of disease remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy

Feng

Chen

et al. 2018

Mol Med Report

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Diabetic nephropathy (DN) is an important microvascular complication of diabetes, and one of the leading causes of end-stage kidney disease. However, the mechanism of the DN pathogenic process remains unclear. Recently, long non-coding (lnc)RNA dysregulation has been regarded to cause the occurrence and development of various human diseases, although the functions of lncRNAs in human DN are poorly understood. The authors' previous study using microarray analysis identified hundreds of dysregulated lncRNAs in DN, although the functions of these lncRNAs were not demonstrated. Out of those dysregulated lncRNAs, Gm5524 was significantly upregulated in response to DN, while Gm15645 was significantly downregulated in response to DN. In the present study, this result was further validated by reverse transcription-quantitative polymerase chain reaction assays, and downregulating or overexpressing Gm5524 and Gm15645 in mouse podocytes. Notably, knockdown of Gm5524 and overexpression of Gm15645 induced mouse podocyte apoptosis and decreased cell autophagy in high-glucose culture conditions. In conclusion, the results of the present study revealed the roles of lncRNAs Gm5524 and Gm15645 in high-glucose induced podocyte apoptosis and autophagy during DN, which may further the understanding of the involvement of lncRNAs in DN, and provide a potential novel therapeutic target for this disease.

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Non-genetic mechanisms of diabetic nephropathy

Cited by 55 publications

References 120 publications

Exploring macrophage cell therapy on Diabetic Kidney Disease

Exploring macrophage cell therapy on Diabetic Kidney Disease

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Dysregulation of lncRNAs GM5524 and GM15645 involved in high‑glucose‑induced podocyte apoptosis and autophagy in diabetic nephropathy

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