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

作者: Masao Toyoda , Daisuke Suzuki , Masashi Honma , Goro Uehara , Takako Sakai

DOI: 10.1111/J.1523-1755.2004.00798.X

关键词:

摘要: High expression of PKC-MAPK pathway mRNAs correlates with glomerular lesions in human diabetic nephropathy. Background Activation protein kinase C (PKC) is a major signaling for transforming growth factor (TGF)-β to induce extracellular matrix (ECM) production nephropathy (DN). PKC also activates mitogen-activated (MAPK), which called the pathway. The probably responsible PKC-related abnormalities glomeruli. To confirm involvement this pathway, we determined localization and glomeruli by situ hybridization method. Methods In present study, examined PKCβ1, MAPK/ERK (MEK) 1, MEK2, signal-regulated (ERK) ERK2, TGF-β1 using renal tissue samples from kidneys affected DN ( N = 21) normal kidney (NHK; 6). We performed an immunohistochemical study anti-phosphorylated MEK1/2 (P-MEK) ERK1/2 (P-ERK) antibodies. severity was classified into three groups according mesangial expansion: D1 4), D2 13), D3 4). analyzed differences correlations between variables. Results glomeruli, number cells that stained these significantly higher than NHK. tended be inversely proportional degree expansion. P-MEK P-ERK signal intensity were parallel its mRNA pattern. Furthermore, there significant among P-MEK, intensity, PKCβ1 expression. Conclusion Our results suggest high plays important role development and/or progression early damage DN.

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