Ang-(1–7) inhibited mitochondrial fission in high-glucose-induced podocytes by upregulation of miR-30a and downregulation of Drp1 and p53

Ma, Lianhuan; Han, Chunlei; Peng, Tao; Li, Naie; Zhang, Bei; Zhen, Xiaowen; Yang, Xiaoling

doi:10.1016/j.jcma.2016.08.006

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…Drp1 overexpression has been widely reported in HG and diabetic conditions. Podocytes and glomerular mesangial cells grown in HG medium exhibit significant Drp1 upregulation and increased mitochondrial fission, which promote podocyte loss and compromise glomerular function, suggesting that elevated Drp1 plays a role in the pathogenesis of diabetic nephropathy [25][26][27]. In addition, Drp1 overexpression was observed in pancreatic β-islet cells grown in HG medium concomitant with increased mitochondrial fission, cytochrome c release, reduced mitochondrial membrane potential, caspase-3 activation, and reactive oxygen species (ROS) production [28].…”

Section: Introductionmentioning

confidence: 99%

Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy

Kim

Sesaki

Roy

2021

Cells

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High glucose (HG)-induced Drp1 overexpression contributes to mitochondrial dysfunction and promotes apoptosis in retinal endothelial cells. However, it is unknown whether inhibiting Drp1 overexpression protects against the development of retinal vascular cell loss in diabetes. To investigate whether reduced Drp1 level is protective against diabetes-induced retinal vascular lesions, four groups of mice: wild type (WT) control mice, streptozotocin (STZ)-induced diabetic mice, Drp1+/− mice, and STZ-induced diabetic Drp1+/− mice were examined after 16 weeks of diabetes. Western Blot analysis indicated a significant increase in Drp1 expression in the diabetic retinas compared to those of WT mice; retinas of diabetic Drp1+/− mice showed reduced Drp1 level compared to those of diabetic mice. A significant increase in the number of acellular capillaries (AC) and pericyte loss (PL) was observed in the retinas of diabetic mice compared to those of the WT control mice. Importantly, a significant decrease in the number of AC and PL was observed in retinas of diabetic Drp1+/− mice compared to those of diabetic mice concomitant with increased expression of pro-apoptotic genes, Bax, cleaved PARP, and increased cleaved caspase-3 activity. Preventing diabetes-induced Drp1 overexpression may have protective effects against the development of vascular lesions, characteristic of diabetic retinopathy.

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Section: Introductionmentioning

confidence: 99%

Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy

Kim

Sesaki

Roy

2021

Cells

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“…Consistent with these findings, Ma et al [ 112 ] found that mice with genetic deletion of the AT2 receptor gene have (1) decreased cortical ACE2 activity, Mas expression, and Ang-(1-7) levels in kidney tissue; (2) increased production of ACE, Ang II, and AT1 receptor in kidney cortex; (3) high BP, increased indices of kidney injury, and mesangial matrix expansion score; and (4) microalbuminuria. Ali et al [ 113 ] showed that AT2 and Mas receptors have molecular interactions, mainly concerning NO release and diuretic responses.…”

Section: Role Of Classical and Alternative Raas Axes In Pediatric Kidmentioning

confidence: 74%

2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus

et al. 2020

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The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counterregulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

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“…In INS1 cells incubated with 20 mmol/l glucose, expression of proteins ( MFN1, MFN2, OPA1, FIS1 , and DRP1 ) is significantly reduced, with the greatest reduction for FIS1 (Schultz et al, 2016). High glucose induces an increase in DRP1 in podocytes (Ma et al, 2016). High glucose and high palmitate increase expression of FIS1 and p- DRP1/DRP1 and decrease expression of MFN2 (Liu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial unfolded protein response gene CLPP changes mitochondrial dynamics and affects mitochondrial function

Xiong

Xiao-jun

et al. 2019

PeerJ

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Mitochondrial dynamics is associated with mitochondrial function, which is associated with diabetes. Although an important indicator of the mitochondrial unfolded protein response, to the best of our knowledge, CLPP and its effects on mitochondrial dynamics in islet cells have not been studied to date. We analyzed the effects of CLPP on mitochondrial dynamics and mitochondrial function in the mice islet β-cell line Min6 under high glucose and high fat conditions. Min6 cells were assigned to: Normal, HG, HG+NC, HG+siCLPP, HF, HF+NC and HF+ siCLPP groups. High glucose and high fat can promote the mRNA and protein expression of CLPP in mitochondria. The increase of mitochondrial fission, the decrese of mitochondrial fusion, and the damage of mintocondrial ultrastructure were significant in the siCLPP cell groups as compared to no-siCLPP treated groups. Meanwhile, mitochondrial functions of MIN6 cells treated with siCLPP were impaired, such as ATP decreased, ROS increased, mitochondrial membrane potential decreased. In addition, cell insulin secretion decreased and cell apoptosis rate increased in siCLPP groups. These results revealed that mitochondrial unfolded protein response geneCLPP alleviated high glucose and high fat-induced mitochondrial dynamics imbalance and mitochondrial dysfunction.

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Ang-(1–7) inhibited mitochondrial fission in high-glucose-induced podocytes by upregulation of miR-30a and downregulation of Drp1 and p53

Abstract: Ang-(1-7) inhibited mitochondrial fission in HG-induced podocytes by upregulation of miR-30a and downregulation of Drp1 and p53.

Cited by 12 publications

References 38 publications

Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy

Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy

2020 update on the renin–angiotensin–aldosterone system in pediatric kidney disease and its interactions with coronavirus

Mitochondrial unfolded protein response gene CLPP changes mitochondrial dynamics and affects mitochondrial function

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