Mesangial deposition of type I collagen in human glomerulosclerosis

Glick, Alan D.; Jacobson, Howard; Haralson, Michael A.

doi:10.1016/0046-8177(92)90057-a

Cited by 57 publications

(32 citation statements)

References 30 publications

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“…Coupled with the consistent inhibition ofAGE-induced changes throughout these experiments, these data lend credence to the postulate that there is a causal link between the presence of AGE moieties within the glomerular ECM and the observed responses. Although interstitial collagen (type I) has been observed in advanced human diabetic glomerular lesions (27) (39,40). The glomerular changes were observed at 4 weeks of AGE administration.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease.

Yang

Vlassara

Peten

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

284

173

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Several lines of evidence suggest that the excessive accumulation of extracellular matrix in the glomeruli of diabetic kidneys may be due to reactive intermediates forming between glucose and matrix proteins called advanced glycation end products (AGEs). Normal mice received AGEmodified mouse serum albumin i.p. for 4 weeks, and glomerular extracellular matrix, growth factor mRNA levels, and morphology were examined. We found that AGE induced an increase in glomerular extraceflular matrix al(IV) collagen, laminin Bi, and transforming growth factor Pis mRNA levels, as measured by competitive PCR, as well as glomerular hypertrophy. The AGE response was specific because the coadministration of an AGE inhibitor, aminoguanidine, reduced all these changes. We conclude that AGEs affected expression of genes implicated in diabetic kidney disease and may play a major role in nephropathy.reactive AGEs, thus preventing AGE-protein cross-linking (14). Among other effects, nG was shown to reduce AGE content of aortic tissue in long-term-diabetic rats (15) and attenuate the glomerular lesions in diabetic rats (16), suggesting that AGEs participate in the development of these lesions. When the response(s) of cultured renal mesangial cells to AGE-albumin was examined, we found that the in vitro expression and secretion of several ECM components were up-regulated through surface receptors (17, 18). Furthermore, normal rats chronically injected with AGE developed vascular dysfunction and glomerular lesions (19,20), which were markedly reduced in those cotreated with nG.

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Section: Discussionmentioning

confidence: 99%

Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease.

Yang

Vlassara

Peten

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

284

173

View full text Add to dashboard Cite

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“…ECM contains different collagen types involved in mesangial expansion (Nerlich and Schleicher, 1991). Recent studies have indicated that hyperglycemia in diabetic nephropathy increases synthesis of ECM components, such as type I and type IV collagen (Glick et al, 1992;Esposito et al, 1996). TGF-␤, a potent fibrogenic factor, stimulates collagen synthesis in cultured stellate cells, and hepatic overexpression of TGF-␤1 in transgenic mice has been shown to cause hepatic fibrosis (Sanderson et al, 1995;Ikeda et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Tranilast Prevents the Progression of Experimental Diabetic Nephropathy through Suppression of Enhanced Extracellular Matrix Gene Expression

Akatsuka¹,

Ota²,

Torita³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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The present study was performed to investigate the effects of the antiallergic drug tranilast on the development of diabetic nephropathy in streptozotocin (50 mg/kg)-induced diabetic spontaneously hypertensive rats (SHR). Diabetic SHR were given standard chow or chow containing tranilast at a dose of 1400 mg/kg for 24 weeks. The effects of tranilast on urinary albumin excretion, mesangial expansion, expression of transforming growth factor-␤ (TGF-␤) and type I collagen mRNAs, number of anionic sites on the glomerular basement membrane (GBM), and urinary TGF-␤ and 8-hydroxy-2Ј-deoxyguanosine (8-OHdG) excretion were assessed. Tranilast did not affect the blood glucose concentration or blood pressure in diabetic SHR. Urinary albumin excretion rate and creatinine clearance were markedly increased in diabetic SHR. Tranilast treatment decreased albuminuria and hyperfiltration. Tranilast inhibited the diabetes-induced expansion of mesangial and tuft areas, as well as the increase in urinary TGF-␤ and 8-OHdG excretion, loss of anionic sites of GBM, and overexpression of TGF-␤ as determined immunohistochemically. The levels of TGF-␤ and type I collagen mRNA expression were increased in the renal cortex in untreated diabetic SHR at 24 weeks, as determined by real-time quantitative polymerase chain reaction. Tranilast treatment inhibited the up-regulation of TGF-␤ and type I collagen mRNA expression by 65 and 36%, respectively, in diabetic SHR. In conclusion, tranilast decreased albuminuria by suppressing glomerular hyperfiltration, mesangial expansion, and loss of the charge barrier via regulation of extracellular matrix gene expression and oxidative stress. Tranilast may be clinically useful in the treatment of diabetic nephropathy.

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“…37 These lesions consist of an accumulation of mesangial matrix with collagen fibrils, small lipid particles, and cellular debris. 39 A completely developed Kimmelstiel-Wilson lesion destroys the normal structure of glomerular tuft with a decrease in mesangial cells, especially in the central area. 37 In 1992, a graphic method of analysis of the position of Kimmelstiel-Wilson lesions demonstrated the nodules were distributed in a horseshoe-shaped area corresponding to the peripheral or intralobular mesangium, 40 excluding the possibility of hyperfiltration as being their main cause of development.…”

Section: Class Iii: Nodular Sclerosis (Kimmelstielwilson Lesions)mentioning

confidence: 99%