Increased intraglomerular thrombin formation in diabetic microangiopathy

Tada, Hayato; Kuboki, Koji; Ôshima, Yasuo; Takeuchi, S; Isogai, Sho

doi:10.1016/0168-8227(89)90102-2

Cited by 6 publications

(4 citation statements)

References 7 publications

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“…Expression and function of the thrombin receptor in the human kidney have been implicated as important regulatory components of glomerular and vascular effects within normal and diseased kidneys [30]. Because the renal thrombin activity is increased in patients with diabetic nephropathy [16,17], thrombin may influence expression of TSP1 in renal disease. In this study, thrombin increased TSP1 mRNA in glomerular epithelial cells within 30 min.…”

Section: Discussionmentioning

confidence: 99%

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Age-Related Expression of Renal Thrombospondin 1 mRNA in F344 Rats: Resemblance to Diabetes-Induced Expression in Obese Zucker Rats

1999

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Age-related increases occurred in renal thrombospondin 1 (TSP1) mRNA in F344 rats, resembling diabetes-induced TSP1 mRNA in the obese Zucker rat. TSP1 mRNA was 3.5-fold higher in 24-month-old than in 3-month-old F344 rats. TSP1 mRNA increased similarly in 5-month-old obese Zucker rats as compard with lean littermates and correlated positively with the extent of proteinuria (r = 0.71). In situ hybridization identified elevated TSP1 mRNA levels in epithelial cells of distended tubules as well as in interstitium near dilated tubules of both 24-month-old F344 rats and 5-month-old obese Zucker rats. Furthermore, thrombin increased TSP1 mRNA in mesangial and epithelial cells in culture, indicating that thrombin may contribute to elevated TSP1 expression in renal disease. Thrombin increased TSP1 mRNA within 30 min after treatment which required de novo synthesis of protein. The thrombin receptor tethered ligand peptide, SFLLRN, increased TSP1 mRNA, indicating that the thrombin-induced increase in TSP1 mRNA was due to direct thrombin receptor (PAR1) stimulation. These results show that increased TSP1 mRNA levels are a component of interstitial fibrosis seen in aged and diabetic kidneys and suggest that similar pathological changes occur in kidneys of aging and diabetic rats.

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Section: Discussionmentioning

confidence: 99%

“…Because increased renal thrombin activity is seen in patients with diabetic nephropathy [16,17], the objective of this study was to determine whether thrombin affects TSP1 mRNA levels in renal cells and to characterize diabetes-and aging-induced changes in renal TSP1 mRNA in Zucker and F344 rats.…”

Section: Introductionmentioning

confidence: 99%

Age-Related Expression of Renal Thrombospondin 1 mRNA in F344 Rats: Resemblance to Diabetes-Induced Expression in Obese Zucker Rats

1999

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“…Because thrombin activity has been demonstrated in patients with renal disease (25,26) and has been implicated in mediating renal remodeling during chronic renal failure (19,(27)(28)(29), the effect of thrombin on Sgk mRNA levels was examined. 4).…”

Section: Resultsmentioning

confidence: 99%

“…The expression and function of the thrombin receptor in the human kidney has been implicated as an important regulatory component of glomerular and vascular effects within the normal and diseased kidney (29). Because renal thrombin activity is increased in patients with diabetic nephropathy (25,26), thrombin may influence the expression of Sgk in renal disease. In this study, we demonstrate that thrombin increased Sgk mRNA in glomerular epithelial cells within 15 min and that thrombin does not affect Sgk mRNA stability.…”

Section: Discussionmentioning

confidence: 99%

Sgk, a Putative Serine/Threonine Kinase, Is Differentially Expressed in the Kidney of Diabetic Mice and Humans

Kumar¹,

Brooks²,

Olson³

et al. 1999

Journal of the American Society of Nephrology

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Abstract. Differential display PCR was used to identify alternate expression of serum glucocorticoid-regulated kinase (Sgk) mRNA in diabetes-induced renal disease. Differential expression of Sgk mRNA was identified in the kidneys of normal and obese db/db mice, a model of select aspects of human diabetic nephropathy. Sgk mRNA was selectively increased in diabetic mouse kidneys. The Sgk mRNA levels remained constant in other tissues from obese db/db mice. An increase in Sgk mRNA was also observed in the human diabetic kidney. In addition, thrombin, which may play a role in the progression of renal disease, increased Sgk message in cell culture. Because the diabetes-induced increase in Sgk was only observed in the kidney, which is particularly susceptible to diabetes-induced damage, Sgk may play a role in diabetic nephropathy.

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Relationship between urinary excretion of fibronectin degradation products and proteinuria in diabetic patients, and their suppression after continuous subcutaneous heparin infusion

Kuboki

Tada

Shin

et al. 1993

Diabetes Research and Clinical Practice

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Increased intraglomerular thrombin formation in diabetic microangiopathy

Cited by 6 publications

References 7 publications

Age-Related Expression of Renal Thrombospondin 1 mRNA in F344 Rats: Resemblance to Diabetes-Induced Expression in Obese Zucker Rats

Age-Related Expression of Renal Thrombospondin 1 mRNA in F344 Rats: Resemblance to Diabetes-Induced Expression in Obese Zucker Rats

Sgk, a Putative Serine/Threonine Kinase, Is Differentially Expressed in the Kidney of Diabetic Mice and Humans

Relationship between urinary excretion of fibronectin degradation products and proteinuria in diabetic patients, and their suppression after continuous subcutaneous heparin infusion

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