title: Early transcriptional regulation by C-peptide in freshly isolated rat proximal tubular cells.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Emma
authors: E
authors: Lindahl
authors: Lina
authors: L
authors: Nordquist
authors: Patrick
authors: P
authors: Müller
authors: Eli
authors: E
authors: El Agha
authors: Malou
authors: M
authors: Friederich
authors: Karin
authors: K
authors: Dahlman-Wright
authors: Fredrik
authors: F
authors: Palm
authors: Hans
authors: H
authors: Jörnvall