PTEN Inhibits High Glucose‐Induced Phenotypic Transition in Podocytes

Xing, Lingxiao; Liu, Qingjuan; Fu, Shanlin; Li, Shaomei; Yang, Lin; Liu, Shuxia; Hao, Jun; Yu, Lianying; Duan, Huijun

doi:10.1002/jcb.25136

Cited by 28 publications

(20 citation statements)

References 34 publications

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“…The FSP1 positive cells selectively expressed Snail and ILK preferentially, which played pivotal roles in inducing EMT. Xing et al [ 26 ] demonstrated that podocyte incubated in elevated glucose levels for 48 h could trigger activation of the PI3K/AKT pathway and elevate protein expressions of α -SMA and desmin. Whereas, protein expressions of podocalyxin and nephrin were suppressed.…”

Section: Pathomechanism Of Podocyte Injurymentioning

confidence: 99%

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Dai

Liu

2017

Journal of Diabetes Research

208

139

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Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases. In this review, we highlight new molecular insights underlying podocyte injury in the progression of DN, which offer new therapeutic targets to develop important renoprotective treatments for DN over the next decade.

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Section: Pathomechanism Of Podocyte Injurymentioning

confidence: 99%

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Dai

Liu

2017

Journal of Diabetes Research

208

139

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“…It should be noted that the slit diaphragm proteins nephrin, CD2AP and podocin, in addition to their structural functions, are able to initiate PI3K/AKT‐dependent signal transduction in glomerular podocytes . It is well known that PI3K/p‐Akt signalling pathway protects glomerular podocytes and ameliorates proteinuria . However, there is no direct evidence to date to conclusively demonstrate that activation of the PI3K/AKT pathway by nephrin in the podocyte protects against apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D3 ameliorates podocyte injury through the nephrin signalling pathway

Trohatou

Tsilibary

Charonis

et al. 2017

J Cellular Molecular Medi

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Renal podocytes form the main filtration barrier possessing unique phenotype maintained by proteins including podocalyxin and nephrin, which are modulated in pathological conditions. In diabetic nephropathy (DN), podocytes become structurally and functionally compromised. Nephrin, a structural backbone protein of the slit diaphragm, acts as regulator of podocyte intracellular signalling with renoprotective role. Vitamin D3 through its receptor, VDR, provides renal protection in DN but limited data exist about its effect on podocytes. In this study, we used isolated rat glomeruli to assess podocalyxin and nephrin expression after treatment with the 1,25‐dihydroxyvitamin D3 analogue paricalcitol in the presence of normal and diabetic glucose levels. The role of 1,25‐dihydroxyvitamin D3 (calcitriol) and its analogue, paricalcitol, on podocyte morphology and survival was also investigated in the streptozotocin (STZ)‐diabetic animal model. In our ex vivo model, glomeruli exhibited high glucose‐mediated down‐regulation of podocalyxin, and nephrin, while paricalcitol reversed the high glucose‐induced decrease of nephrin and podocalyxin expression. Paricalcitol treatment enhanced VDR expression and promoted VDR and RXR co‐localization in the nucleus. Our data also indicated that hyperglycaemia impaired survival of cultured glomeruli and suggested that the implemented nephrin down‐regulation was reversed by paricalcitol treatment, initiating Akt signal transduction which may be involved in glomerular survival. Our findings were further verified in vivo, as in the STZ‐diabetic animal model, calcitriol and paricalcitol treatment resulted in significant amelioration of hyperglycaemia and restoration of nephrin signalling, suggesting that calcitriol and paricalcitol may provide molecular bases for protection against loss of the permselective renal barrier in DN.

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“…Podocyte foot processes and the hiatus of the diaphragm cover the surface of the GBM, maintaining a large filtration area, which is the last barrier for preventing protein leakage into the urine. 27 Studies have shown that structural and functional damage of podocytes occur in the early stage of DN, and a series of functional and morphological changes occur, including hypertrophy of podocytes, 28 epithelial mesenchymal transdifferentiation of podocytes, 29 detachment of podocytes 23 and apoptosis of podocytes. 30,31 The absence of characteristic proteins in podocytes results in an increase in pore space, destruction of the glomerular filtration barrier and a gradual decline in renal function.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia in rats

Xiong

Fang

et al. 2020

J Int Med Res

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This study aimed to investigate whether luteolin delays the progress of diabetic nephropathy (DN) induced by streptozotocin. Methods: Fifty-three healthy, 8-week-old, male Sprague-Dawley rats were randomly divided into the control (n ¼ 6), model (n ¼ 23), and experimental groups (n ¼ 24). The rat model of diabetic nephropathy was established by intraperitoneal injection of streptozotocin. Rats in the experimental group were administered luteolin suspension of 80 mg/kg daily for 8 weeks. Blood glucose levels and body weight were recorded until the fourth week. After intragastric administration, blood flow and the protective effect of luteolin on diabetic nephropathy were evaluated. Results: The degree of renal apoptosis and fibrosis in the experimental group was milder, and glomerular structure was more complete compared with the model group. Nphs2 staining suggested that luteolin delayed apoptosis and deletion and fusion of podocytes under high glucose levels, and protected the filtration function of the basement membrane by upregulating Nphs2 protein expression. Time intensity curve results suggested that luteolin delayed deterioration of renal haemodynamics under hyperglycaemia. Conclusions: This study shows that luteolin delays progression of diabetic nephropathy. This drug has potential wide applicability in future clinical application.

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PTEN Inhibits High Glucose‐Induced Phenotypic Transition in Podocytes

Cited by 28 publications

References 34 publications

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Vitamin D3 ameliorates podocyte injury through the nephrin signalling pathway

Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia in rats

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