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Early transcriptional regulation by C‐peptide in freshly isolated rat proximal tubular cells
Author(s) -
Lindahl Emma,
Nordquist Lina,
Müller Patrick,
El Agha Eli,
Friederich Malou,
DahlmanWright Karin,
Palm Fredrik,
Jörnvall Hans
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1220
Subject(s) - transcription (linguistics) , gene expression , proinsulin , peptide , gene , biology , microbiology and biotechnology , reverse transcription polymerase chain reaction , regulation of gene expression , transcription factor , receptor , gene expression profiling , chemistry , biochemistry , endocrinology , diabetes mellitus , philosophy , linguistics
Abstract Background Clinical studies have shown that proinsulin C‐peptide exerts renoprotective effects in type 1 diabetes, although the underlying mechanisms are poorly understood. As C‐peptide has been shown to induce several intracellular events and to localize to nuclei, we aimed to determine whether gene transcription is affected in proximal tubular kidney cells, and if so, whether the genes with altered transcription include those related to protective mechanisms. Methods The effect of C‐peptide incubation (2 h) on gene expression was investigated in freshly isolated proximal tubular cells from streptozotocin‐diabetic Sprague‐Dawley rats using global gene expression profiling and real‐time quantitative polymerase chain reaction. Protein expression was assayed using western blotting. Different bioinformatic strategies were employed. Results Gene transcription profiling demonstrated differential transcription of 492 genes ( p < 0.01) after 2 h of C‐peptide exposure, with the majority of these genes repressed (83%). Real‐time quantitative polymerase chain reaction validation supported a trend of several G protein‐coupled receptors being activated, and certain transcription factors being repressed. Also, C‐peptide repressed the transcription of genes associated with the pathways of circulatory and inflammatory diseases. Conclusion This study shows that C‐peptide exerts early effects on gene transcription in proximal tubular cells. The findings also bring further knowledge to the renoprotective mechanisms of C‐peptide in type 1 diabetes, and support a transcriptional activity for C‐peptide. It is suggested that C‐peptide may play a regulatory role in the gene expression of proximal tubular cells. Copyright © 2011 John Wiley & Sons, Ltd.