title: PDGF-α stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat.
abstract: 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-α 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-α rats underwent bowel transection and were treated with PDGF-α, SBS rats underwent a 75% bowel resection, and SBS-PDGF-α rats underwent bowel resection and were treated with PDGF-α. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined at euthanasia. Illumina's Digital Gene Expression analysis was used to determine PDGF-related gene expression profiling. PDGF-α and PDGF-α receptor (PDGFR-α) expression was determined by 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-α and PDGFR-α expression in jejunum and ileum compared with sham animals. SBS-PDGF-α rats demonstrated a significant increase in bowel and mucosal weight, villus height, and crypt depth in jejunum and ileum compared with SBS animals. PDGF-α receptor expression in crypts increased in SBS rats (vs. sham) and was accompanied by an increased cell proliferation following PDGF-α 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-α stimulates enterocyte turnover, which is correlated with upregulated PDGF-α receptor expression in the remaining small intestine.
authors.affiliation: Technion-Israel Institute of Technology, the Ruth and Bruce Rappaport Faculty of Medicine, Laboratory of Intestinal Adaptation and Recovery, Bnai Zion Medical Center, Haifa, Israel. igor-dr@internet-zahav.net
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Mogilner
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pollak
authors.forename: Shiri
authors.initials: S
authors.lastname: Blumenfeld
authors.forename: Jacob
authors.initials: J
authors.lastname: Bejar
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D012778:Short Bowel Syndrome / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; D051028:bcl-2-Associated X Protein; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha