Platelet-derived growth factor-alpha (PDGF-a) stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat

Numerous cytokines have been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal interaction. Growing evidence suggests that platelet-derived growth factor (PDGF) signaling is an important mediator of these interactions. The purpose of this study was to evaluate the effect of PDGF-a on enterocyte turnover in a rat model of short bowel syndrome (SBS). Male rats were divided into four groups: Sham rats underwent bowel transection, Sham-PDGF-a rats underwent bowel transection and were treated with PDGF-a, SBS rats underwent a 75% bowel resection, and SBS-PDGF-a rats underwent bowel resection and were treated with PDGF-a. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at sacrifice. Illumina's Digital Gene Expression (DGE) analysis was used to determine PDGF-related gene expression profiling. PDGF-a and PDGF-a receptor (PDGFR-a) expression was determined using Real Time PCR. Western blotting was used to determine p-ERK, Akt1/2/3, bax and bcl-2 protein levels. SBS rats demonstrated a significant increase in PDGF-a and PDGFR-a expression in jejunum and ileum compared to sham animals. SBS-PDGF-a rats demonstrated a significant increase in bowel and mucosal weight, villus height and crypt depth in jejunum and ileum compared to SBS animals. PDGF-a expression in crypts increased in SBS rats (vs sham) and was accompanied by increased cell proliferation following PDGF-a administration. A significant decrease in cell apoptosis in this group was correlated with lower bax protein levels. In conclusion, in a rat model of SBS, PDGF-a stimulates enterocyte turnover, which is correlated with up-regulated PDGF-a receptor expression in the remaining small intestine.