Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells

Kitsiou, Paraskevi V.; Τzinia, Athina K.; Stetler-Stevenson, William G.; Michael, Alfred F.; Fan, Wei; Zhou, Bing; Tsilibary, Effie C.

doi:10.1152/ajprenal.00266.2002

Cited by 87 publications

(77 citation statements)

References 48 publications

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“…Our data suggest that plasma MMP-2 (~70 kDa) is decreased in DKA, possibly due to the hyperglycemic conditions that are characteristic of DKA (25). Decreased MMP-2 facilitates increased extracellular matrix deposition in vascular structures as a primary function of MMP-2 is extracellular matrix turnover (26).…”

Section: Mmps In Pediatric Dkamentioning

confidence: 77%

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis

Woo

Patterson²,

Cepinskas

et al. 2015

Pediatr Res

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Background: Diabetic ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived matrix metalloproteinases (MMPs) from DKA patients and to correlate plasma MMP concentrations with DKA severity. Methods: Plasma was obtained from children with type 1 diabetes, either in DKA (n = 16) or insulin controlled (CON; n = 16). Antibody microarray and gelatin zymography were used to quantify plasma MMPs and their endogenous tissue inhibitors (TIMPs). MMP concentrations were correlated with DKA severity (blood pH). Quantitative PCR of leukocyte mRNA was used to help determine the origin of plasma MMPs. results: DKA was associated with altered plasma levels of ↓MMP-2 (P < 0.001), ↑MMP-8 (P < 0.001), ↑MMP-9 (P < 0.05), and ↑TIMP-4 (P < 0.001), as compared with CON. Elevated MMP-8 and MMP-9 were both positively correlated with DKA severity (P < 0.05). DKA was associated with increased leukocyte mRNA for MMP-8, MMP-9, and TIMP-4 (P < 0.005). conclusion: MMPs are dynamically regulated during DKA. Plasma MMP-8 and MMP-9 concentrations correlate with DKA severity and are known to degrade brain microvascular endothelial cell tight junctions. Thus, leukocyte-derived MMPs might contribute to DKA-associated cerebrovascular complications.

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Section: Mmps In Pediatric Dkamentioning

confidence: 77%

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis

Woo

Patterson²,

Cepinskas

et al. 2015

Pediatr Res

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“…It has been reported in streptozotocindiabetic rats, that the expression of α3β1 integrin, which is the main integrin occurring at the interface between the foot process and the GBM, was decreased in comparison to the normal control rate [9,10]. Accordingly, glomerular epithelial cells cultured in high glucose showed reduced expression of the α3, α2, and β1 integrin subunits in combination with increased expression of α5 and αvβ3 integrins [7]. An increase of the αv integrin subunit was also observed in situ, in podocytes in glomeruli of diabetic rats, compared to normal control rats [11].…”

Section: Glomerular Basement Membrane (Gbm)mentioning

confidence: 92%

“…We have studied interactions between glomerular epithelial cells and their underlying matrix in vitro. In the presence of an increased glucose concentration (25 mM), the cells adhered less to collagen IV, a major component of the GBM, than glomerular epithelial cells grown at normal glucose concentration (5 mM) [7]. At normal glucose concentration, the interaction with collagen IV was mediated mainly by the α3β1 and α2β1 and to a lesser extent by α5β1 integrins, whereas at high glucose concentration the expression of αvβ3 and α5β1 integrins was upregulated ( Figure 2) [7,8].…”

Section: Glomerular Basement Membrane (Gbm)mentioning

confidence: 97%

“…In the presence of an increased glucose concentration (25 mM), the cells adhered less to collagen IV, a major component of the GBM, than glomerular epithelial cells grown at normal glucose concentration (5 mM) [7]. At normal glucose concentration, the interaction with collagen IV was mediated mainly by the α3β1 and α2β1 and to a lesser extent by α5β1 integrins, whereas at high glucose concentration the expression of αvβ3 and α5β1 integrins was upregulated ( Figure 2) [7,8]. It has been reported in streptozotocindiabetic rats, that the expression of α3β1 integrin, which is the main integrin occurring at the interface between the foot process and the GBM, was decreased in comparison to the normal control rate [9,10].…”

Section: Glomerular Basement Membrane (Gbm)mentioning

confidence: 97%

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Microvascular basement membranes in diabetes mellitus

Tsilibary

2003

The Journal of Pathology

241

156

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The alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia-induced alteration of the pattern of podocyte-integrin expression, decreased expression of matrix metalloproteinases (MMP-2 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti-VEGF antibodies attenuates glomerular basement membrane thickening, platelet-derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation endproducts but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified.

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“…It was reported in literature that the expression of MMP-2 was decreased by 25mmol/L glucose, but the expression of TIMP-2, the special inhibitor of TIMP-1, was upregulated, which promoted ECM sidiment in the cultured human glomerular epithelial cells [5]. Berthier CC et al [6] found that the expression of MMP-2 and its inhibitor TIMP-2 and mRNA of TGF increased significantly in chronic rejection animal model of Fisher and Lewis mouse.…”

Section: Discussionmentioning

confidence: 99%

Expression of MMP-2 and TIMP-1 in Renal Tissue of Patients with Chronic Active Antibody-mediated Renal Graft Rejection

Yan¹,

Sui²,

Wang³

et al. 2012

Diagn Pathol

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ObjectiveTo investigate the expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metallopropteinase-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (AMR), and to explore their role in the pathogenesis of AMR.MethodsImmunohistochemistry assay and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts with interstitial fibrosis and tubular atrophy (IF/TA) in 46 transplant recipients and 15 normal renal tissue specimens as the controls. The association of the expression level of either MMP-2 or TIMP-1 with the pathological grade of IF/TA in AMR was analyzed.ResultsThe expression of either MMP-2 or TIMP-1 was significantly increased in the renal allografts of the recipients as compared with the normal renal tissue (P < 0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased along with the increase of pathological grade of IF/TA (P < 0.05). In IF/TA groups, the expression of TIMP-1 was positively correlated to serum creatinine level (r = 0.718, P < 0.05).ConclusionsIt is suggested by the results that abnormal expressions of MMP-2 and TIMP-1 might play roles in the development of renal fibrosis in chronic AMR.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1128474926172838

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Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells

Cited by 87 publications

References 48 publications

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis

Microvascular basement membranes in diabetes mellitus

Expression of MMP-2 and TIMP-1 in Renal Tissue of Patients with Chronic Active Antibody-mediated Renal Graft Rejection

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