High expression of PKC-MAPK pathway mRNAs correlates with glomerular lesions in human diabetic nephropathy

Abstract

Our results suggest that high expression of PKC-MAPK pathway mRNAs plays an important role in the development and/or progression of early tissue damage in DN.

Increased renal gene transcription of protein kinase C-β in human diabetic nephropathy: relationship to long-term glycaemic control

“…In the present study, performed using biopsies from patients with advanced diabetic nephropathy, PKC-β was localised predominantly to tubular epithelial cells. These findings are consistent with the recent findings of Toyoda et al [15], who reported an increase in glomerular PRKC-β mRNA in early diabetic nephropathy, but not in patients with advanced disease. In our study of patients with relatively advanced disease, we also did not find increased glomerular PKC-β expression by immunohistochemistry.…”

“…However, in addition to allosteric modification, a number of in vitro studies have shown that high glucose levels not only change PKC activity, but also increase PKC protein [12,13]. Increases in PKC-β protein levels have also been demonstrated in the in vivo context in rodent models of diabetic nephropathy [14], with more recent studies also showing increased PRKC-β (also known as PRKCB) expression [15]. In this study, we sought to determine the role of PRKC-β transcription in the subsequent amplified activation that has been demonstrated in several models of diabetic nephropathy.…”

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

“…We also demonstrated that BNP effectively inhibited ERK phosphorylation, as well as TGF-β expression, in cultured mesangial cells under high glucose conditions (Figs 7, 8). High glucose conditions activate PKC, and ERK activation occurs through a PKC-dependent mechanism [31,37]. BNP also attenuated PKC-induced phosphorylation of ERK.…”

“…Renal ERK activation Accumulating evidence indicates that activation of the ERK/MAPK signalling pathway plays a key role in the induction of Tgfb1 and extracellular matrix accumulation in diabetic nephropathy [29][30][31]. To address the mechanisms by which Tgfb1 and matrix gene expression was inhibited in BNP-Tg mice, we investigated the phosphorylation of ERK in the kidney.…”

Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)

“…ERK phosphorylation, and thereby activation, is increased in glomeruli and podocytes in response to angiotensin II infusion (49 -52), salt-sensitive hypertension (53), puromycin aminoglycoside nephropathy (54 -58), passive Heymann nephritis (59,60), rapidly progressive glomerulonephritis (61)(62)(63)(64), and diabetic nephropathy (65)(66)(67). Phospho-ERK levels in mesangial cells have been correlated with glomerular damage in IgA nephropathy (68).…”