Thiamine and benfotiamine prevent apoptosis induced by high glucose-conditioned extracellular matrix in human retinal pericytes

2009 ◽  
Vol 25 (7) ◽  
pp. 647-656 ◽  
Author(s):  
Elena Beltramo ◽  
Konstantin Nizheradze ◽  
Elena Berrone ◽  
Sonia Tarallo ◽  
Massimo Porta
Keyword(s):  
Extracellular Matrix ◽  
High Glucose ◽  
Retinal Pericytes ◽  
Human Retinal Pericytes

scholarly journals High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Jinhua Gan ◽  
Maomao Huang ◽  
Genyin Lan ◽  
Li Liu ◽  
Fangyuan Xu
Keyword(s):  
High Glucose ◽  
Pore Formation ◽  
Caspase 3 ◽  
Vision Loss ◽  
Time Dependent ◽  
Dependent Manner ◽  
Caspase 1 ◽  
Retinal Pericytes ◽  
High Glucose Medium ◽  
Human Retinal Pericytes

Diabetic retinopathy (DR) is one of the hallmark complications of diabetes and a leading cause of vision loss in adults. Retinal pericyte death seems to be a prominent feature in the onset of DR. Pyroptosis is an inflammatory form of programmed cell death, defined as being caspase-gasdermin-D (GSDMD)-dependent. The NOD-like receptor pyrin 3 (NLRP3) inflammasome plays an important role in mediating GSDMD activation. However, the role and mechanism of pyroptosis in the loss of retinal pericytes during the pathogenesis of DR are still unclear. In the present study, we cultured primary human retinal pericytes (HRPs) in high glucose medium; caspase-3 inhibitor DEVD, caspase-1 inhibitor YVAD, or NLRP3 inhibitor glyburide was used as intervention reagents; GSDMD was overexpressed or suppressed by transfection with an expressing vector or retroviral silencing of GSDMD, respectively. Our data showed that high glucose induced NLRP3-caspase-1-GSDMD activation and pore formation in a dose- and time-dependent manner (p<0.05) and resulted in the inflammatory cytokines IL-1β and IL-18 and lactate dehydrogenase (LDH) release from HRPs (p<0.05), which are all signs of HRP pyroptosis. Overexpression of GSDMD facilitated high glucose-induced pyroptosis (all p<0.05). However, these effects were blunted by synergistically treating DEVD, YVAD, and silencing GSDMD (p<0.05). Taken together, our results firstly revealed that high glucose induced the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis.

267-OR: Cardiomyocyte Insulin Resistance Manifests on High-Glucose Fibroblast-Derived Extracellular Matrix

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 267-OR
Author(s):  
STEPHAN NIEUWOUDT ◽  
XINMING WANG ◽  
SUBHADIP SENAPATI ◽  
PAUL PARK ◽  
SAM SENYO
Keyword(s):  
Insulin Resistance ◽  
Extracellular Matrix ◽  
High Glucose

Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium

1991 ◽  
Vol 260 (2) ◽  
pp. F185-F191 ◽  
Author(s):  
S. H. Ayo ◽  
R. A. Radnik ◽  
W. F. Glass ◽  
J. A. Garoni ◽  
E. R. Rampt ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Synthesis ◽  
High Glucose ◽  
Mesangial Cells ◽  
Matrix Proteins ◽  
Cell Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Glomerular Mesangium

Nodular expansion of glomerular mesangium with increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50–60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulse-chase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S [( 35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in approximately 40–50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Adenosine A1 Receptor Deficiency Aggravates Extracellular Matrix Accumulation in Diabetic Nephropathy through Disturbance of Peritubular Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Dongli Tian ◽  
Jiaying Li ◽  
Linfeng Zou ◽  
Min Lin ◽  
Xiaoxiao Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Immunohistochemical Staining ◽  
Adenosine A1 Receptor ◽  
Pronounced Increase ◽  
Matrix Deposition ◽  
Adenosine A1 ◽  
Proximal Tubular ◽  
A1 Receptor

Background. We previously observed that adenosine A1 receptor (A1AR) had a protective role in proximal tubular megalin loss associated with albuminuria in diabetic nephropathy (DN). In this study, we aimed to explore the role of A1AR in the fibrosis progression of DN. Methods. We collected DN patients’ samples and established a streptozotocin-induced diabetes model in wild-type (WT) and A1AR-deficient (A1AR-/-) mice. The location and expression of CD34, PDGFRβ, and A1AR were detected in kidney tissue samples from DN patients by immunofluorescent and immunohistochemical staining. We also analyzed the expression of TGFβ, collagen (I, III, and IV), α-SMA, and PDGFRβ using immunohistochemistry in WT and A1AR-/- mice. CD34 and podoplanin expression were analyzed by Western blotting and immunohistochemical staining in mice, respectively. Human renal proximal tubular epithelial cells (HK2) were cultured in medium containing high glucose and A1AR agonist as well as antagonist. Results. In DN patients, the expression of PDGFRβ was higher with the loss of CD34. The location of PDGFRβ and TGFβ was near to each other. The A1AR, which was colocalized with CD34 partly, was also upregulated in DN patients. In WT-DN mice, obvious albuminuria and renal pathological leisure were observed. In A1AR-/- DN mice, more severe renal tubular interstitial fibrosis and more extracellular matrix deposition were observed, with lower CD34 expression and pronounced increase of PDGFRβ. In HK2 cells, high glucose stimulated the epithelial-mesenchymal transition (EMT) process, which was inhibited by A1AR agonist. Conclusion. A1AR played a critical role in protecting the tubulointerstitial fibrosis process in DN by regulation of the peritubular microenvironment.

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