Regulation of Mesangial Cell Alpha-Smooth Muscle Actin Expression in 3-Dimensional Matrix by High Glucose and Growth Factors

Whiteside, Catharine; Munk, Snezana; Ispanovic, Eric; Wang, Hong; Goldberg, Harry; Kapùs, András; Xia, Ling

doi:10.1159/000142099

Cited by 8 publications

(6 citation statements)

References 70 publications

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“…The increased Ca 2+ is in turn needed by other proteins found in the reticuloplasm like GRP78 or PDIA3 [ 29 ]. These observations of regulated changes in actin cytoskeletal protein and calcium binding protein expression, when taken together, are consistent with the known responses of mesangial cells to HG under more chronic conditions [ 30 , 31 ].…”

Section: Discussionsupporting

confidence: 87%

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

Barati

Gould

Salyer

et al. 2016

Journal of Diabetes Research

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The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG) growth conditions as compared to isoosmotic/normal glucose control (NG⁎) conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1) proteins involved in cell survival/cell signaling and (2) proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB), supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase), suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis.

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Section: Discussionsupporting

confidence: 87%

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

Barati

Gould

Salyer

et al. 2016

Journal of Diabetes Research

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“…Accumulating evidence suggests that increased pericyte proliferation has a fundamental role in the pathological processes of fibrosis, inflammation, thrombosis and vessel calcification . Studies have shown that pericytes transdifferentiate into myofibroblasts under profibrotic stimulations . Recent studies have also demonstrated endothelial HIF hydroxylase system plays a critical role in vascular remodelling .…”

Section: Discussionmentioning

confidence: 99%

Ablation of endothelial prolyl hydroxylase domain protein‐2 promotes renal vascular remodelling and fibrosis in mice

Wang

Zeng

Chen

et al. 2017

J Cellular Molecular Medi

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Accumulating evidence demonstrates that hypoxia‐inducible factor (HIF‐α) hydroxylase system has a critical role in vascular remodelling. Using an endothelial‐specific prolyl hydroxylase domain protein‐2 (PHD2) knockout (PHD2ECKO) mouse model, this study investigates the regulatory role of endothelial HIF‐α hydroxylase system in the development of renal fibrosis. Knockout of PHD2 in EC up‐regulated the expression of HIF‐1α and HIF‐2α, resulting in a significant decline of renal function as evidenced by elevated levels of serum creatinine. Deletion of PHD2 increased the expression of Notch3 and transforming growth factor (TGF‐β1) in EC, thus further causing glomerular arteriolar remodelling with an increased pericyte and pericyte coverage. This was accompanied by a significant elevation of renal resistive index (RI). Moreover, knockout of PHD2 in EC up‐regulated the expression of fibroblast‐specific protein‐1 (FSP‐1) and increased interstitial fibrosis in the kidney. These alterations were strongly associated with up‐regulation of Notch3 and TGF‐β1. We concluded that the expression of PHD2 in endothelial cells plays a critical role in renal fibrosis and vascular remodelling in adult mice. Furthermore, these changes were strongly associated with up‐regulation of Notch3/TGF‐β1 signalling and excessive pericyte coverage.

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“…The effects of an ARB on glomerular sclerosis may be dependent on complex interactions between several factors that mediate mesangial matrix expansion. Several cell culture studies have indicated that high glucose-induced mesangial cellular injury cannot be completely blocked by ARBs [35,36]. Fioretto et al .…”

Section: Discussionmentioning

confidence: 99%

Regression of superficial glomerular podocyte injury in type 2 diabetic rats with overt albuminuria: effect of angiotensin II blockade

Ihara

Kiyomoto

Kobori

et al. 2010

Journal of Hypertension

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Objective-Clinical studies indicate that the remission, regression or both of nephrotic-range albuminuria are exerted by angiotensin II receptor blockers (ARBs) in diabetes. The current study was performed to test the hypothesis that these effects of ARBs are associated with regression of glomerular podocyte injury.Methods-We examined the effects of an ARB, olmesartan, on glomerular podocyte injury in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty rats with overt albuminuria.Results-At baseline (55-week-old), diabetic Otsuka-Long-Evans-Tokushima-Fatty rats showed severe albuminuria with desmin-positive areas (an index of podocyte injury) in both superficial and juxtamedullary glomeruli, and podocyte injury was much greater in juxtamedullary than in superficial glomeruli. At 75-week-old, Otsuka-Long-Evans-Tokushima-Fatty rats had developed more severe albuminuria and superficial glomerular podocyte injury, whereas juxtamedullary glomerular podocyte injury did not advance further. Olmesartan (10 mg/kg per day) decreased albuminuria and superficial glomerular desmin staining to levels that were lower than those at baseline, whereas advanced juxtamedullary glomerular podocyte injury was not changed. Conclusion-The current study demonstrates for the first time that juxtamedullary glomerular podocyte injury reaches a severe condition at an earlier time than superficial glomerular podocyte injury during the progression of overt albuminuria in type 2 diabetic rats. Our data also support the hypothesis that the antialbuminuric effects of ARBs are associated with regression of superficial glomerular podocyte injury in type 2 diabetes with nephrotic-range albuminuria.Correspondence to Akira

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Regulation of Mesangial Cell Alpha-Smooth Muscle Actin Expression in 3-Dimensional Matrix by High Glucose and Growth Factors

Cited by 8 publications

References 70 publications

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

Ablation of endothelial prolyl hydroxylase domain protein‐2 promotes renal vascular remodelling and fibrosis in mice

Regression of superficial glomerular podocyte injury in type 2 diabetic rats with overt albuminuria: effect of angiotensin II blockade

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