2003
DOI: 10.1152/ajprenal.00158.2002
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Abstract: Diabetic nephropathy is characterized by the rapid onset of hypertrophy and ECM expansion. Previously, we showed that calcineurin phosphatase is required for hypertrophy and ECM synthesis in cultured mesangial cells. Therefore, we examined the effect of calcineurin inhibition on renal hypertrophy and ECM accumulation in streptozotocin-induced diabetic rats. After 2 wk of diabetes, calcineurin protein was increased in whole cortex and glomeruli in conjunction with increased phosphatase activity. Daily administr… Show more

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Cited by 67 publications
(89 citation statements)
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“…24,25 It has been reported that in the early stage of diabetes, CaN protein is increased in the whole cortex and glomeruli in conjunction with increased phosphatase activity. 9 The CaN/ NFATc pathway was thought to play an important role in TGF-b-mediated induction of glomerular hypertrophy and FN expression, which is in agreement with other literature reporting that administration of CaN inhibitor CsA blocked accumulation of both CaN protein and CaN activity and substantially reduced ECM accumulation and hypertrophy in diabetic glomeruli. 10,11 We have found that NCTD can alleviate the expression of CaN in tubules in DN.…”
Section: Effects Of Can Sirna On Can Mrna and Protein Expression Of Hsupporting
confidence: 90%
See 1 more Smart Citation
“…24,25 It has been reported that in the early stage of diabetes, CaN protein is increased in the whole cortex and glomeruli in conjunction with increased phosphatase activity. 9 The CaN/ NFATc pathway was thought to play an important role in TGF-b-mediated induction of glomerular hypertrophy and FN expression, which is in agreement with other literature reporting that administration of CaN inhibitor CsA blocked accumulation of both CaN protein and CaN activity and substantially reduced ECM accumulation and hypertrophy in diabetic glomeruli. 10,11 We have found that NCTD can alleviate the expression of CaN in tubules in DN.…”
Section: Effects Of Can Sirna On Can Mrna and Protein Expression Of Hsupporting
confidence: 90%
“…CaN is a calcium/calmodulindependent serine/threonine phosphatase that participates in a number of cellular processes and Ca 2 þ -dependent signal transduction pathways. Gooch et al [9][10][11] demonstrated that CaN expression was increased in the diabetic kidney and played an important role in the progression of glomerulosclerosis in DN. In addition, inhibition of CaN by cyclosporine (CsA) could reduce glomerular hypertrophy and block extracellular matrix (ECM) accumulation, such as fibronectin (FN), collagen IV (ColIV), and so on, in glomuruli.…”
mentioning
confidence: 99%
“…To verify that the observed 45-kDa band represented cleaved CaN, we used a second well characterized antibody recognizing a different region of the protein (15,36). The first antibody (Transduction Laboratories, no.…”
Section: Resultsmentioning
confidence: 99%
“…Although renal function was not determined, serum creatinine levels were significantly lower in mice that received the TGF-␤ antibody than in untreated mice, suggesting that neutralization of TGF-␤, in addition to expected reduction in renal fibrosis, also improved renal function by a mechanism that remains to be determined. Previous studies in cultured mesangial cells (23) and in rats with diabetic nephropathy (22) have shown that TGF-␤ upregulation induced glomerular injury through activation of calcineurin, which in turn induced greater NFAT translocation to the nucleus, resulting in mesangial proliferation and extracellular matrix (ECM) accumulation. In the diabetic rats, these effects were reduced by CsA administration in the glomerular but not in tubulointerstitial area (22), suggesting that calcineurin activation promotes ECM accumulation in the glomerulus.…”
Section: Strategies To Prevent or Reduce Chronic Csa Nephrotoxicitymentioning
confidence: 99%