Accelerated Intestinal Epithelial Cell Turnover Correlates with Stimulated BMP Signaling Cascade following Intestinal Ischemia–Reperfusion in a Rat

Abstract

Introduction Bone morphogenetic proteins (BMPs) are a family of proteins that regulate proliferation and differentiation of intestinal epithelial cells. The purpose of this study was to evaluate the role of BMP signaling following intestinal ischemia–reperfusion (IR) in a rat model. Materials and Methods Male Sprague-Dawley rats were divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were sacrificed 24 or 48 hours later, respectively; IR-24 and IR-48 rats underwent occlusion of superior mesenteric artery and portal vein for 30 minutes followed by 24 or 48 hours of reperfusion, respectively. Enterocyte proliferation and apoptosis were determined at sacrifice. BMP-related genes and protein expression were determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry for 48 hours followed by IR. Results IR rats demonstrated a significant increase in BMP2 (twofold increase, p < 0.05), BMP4 (sevenfold increase), STAT3 (70% increase), BMPR1 (70% increase) messenger ribonucleic acid levels in jejunum and was accompanied by a significant increase in BMP2 and BMP4 protein levels in jejunum (sixfold increase) (Western blot) and upward increase in the number of BMP-positive cells (by immunohistochemistry) in jejunal (48% increase) and ileal (56% increase) villi compared with Sham-48 animals. Elevation in BMP2 and BMP4 levels was associated with increased rates of cell proliferation and increased cell apoptosis. Conclusion Forty-eight hours following intestinal IR in rats, BMP signaling pathway was stimulated. The increase in BMP signaling pathway activity correlates with accelerated cell turnover.

Microbial short-chain fatty acids: a bridge between dietary fibers and poultry gut health — A review

“…While the absorptive Alpi + , Lgr5enterocytes move up toward the villus until they reach the villus tip where they go through apoptosis and shed themselves into the lumen to balance defensive barrier under different physiological conditions [43] (Figure 1). This process of turnover lasts for two to five days followed by a bone morphogenetic protein (BMP) sig naling pathway [44].…”

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“…Furthermore, several genes upregulated in M cells compared to Caco-2-cl1 cells were previously reported to play a role in the differentiation of IECs. Among these genes, BMP2 (bone morphogenetic protein 2) encodes a protein that promotes the differentiation of mature colonocytes [53] and is associated with increased epithelial cell turnover following intestinal ischemia-reperfusion in rats [54]. Similarly, an increased density of insulin-like growth factor 1 receptor, encoded by IGF1R gene, has been shown upon the differentiation of intestinal epithelial Caco-2 cells [55].…”

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“…These signaling pathways include Wnt/β-catenin, Hedgehog, Bone morphogenetic protein (BMP) and Notch [9]. Our research group has demonstrated that 24h following IR, Hedgehog [10] and BMP [11] signaling pathways were inhibited, which correlated with inhibited cell turnover. Signs of intestinal recovery appeared 48h after IR and were then correlated with activated Hedgehog and BMP signaling pathways.…”