Sukhotnik I, Dorfman T, Halabi Salim, Pollak Y, Kreizman Shefer H, Coran A G, Berkowitz D
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, Haifa, 31048, Israel.
Pediatr Surg Int. 2016 Dec;32(12):1133-1140. doi: 10.1007/s00383-016-3969-z. Epub 2016 Sep 19.
The hedgehog (Hh) signaling pathway is one of the key regulators of gastrointestinal tract development. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of intestinal stem cells. The purpose of this study was to evaluate the role of Hh signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).
Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75 % bowel resection. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression analysis was used to determine the Hh signaling gene expression profiling. Hh-related genes and protein expression were determined using Real-Time PCR, Western blotting, and immunohistochemistry.
Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 13 genes related to Hh signaling were investigated. In jejunum, eight genes were down-regulated, three genes up-regulated, and two genes remained unchanged. In ileum, five genes were down-regulated and six genes were unchanged in SBS vs sham animals. SBS rats also demonstrated a significant three- to fourfold decrease in SMO, GIL, and PTCH mRNA, and protein levels (determined by Real-Time PCR and Western blot) compared to control animals.
Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by an inhibited Hh signaling pathway. Hh signaling may serve as an important mediator of reciprocal interactions between the epithelium and the underlying mesenchymal stroma during intestinal adaptation following massive bowel resection in a rat.
刺猬信号通路（Hh）是胃肠道发育的关键调节因子之一。最近的研究指出刺猬信号在调节参与肠道干细胞维持和再生的成体干细胞中的作用。本研究的目的是评估Hh信号在短肠综合征（SBS）大鼠模型肠道适应过程中的作用。
雄性大鼠分为两组：假手术组大鼠接受肠横断术，SBS组大鼠接受75%肠切除术。术后2周测定肠道适应参数、肠上皮细胞增殖和凋亡情况。使用Illumina的数字基因表达分析来确定Hh信号基因表达谱。使用实时PCR、蛋白质印迹法和免疫组织化学法测定与Hh相关的基因和蛋白质表达。
大规模小肠切除导致肠上皮细胞增殖显著增加，同时细胞凋亡也增加。从总共20,000个探针中，研究了13个与Hh信号相关的基因。在空肠中，8个基因下调，3个基因上调，2个基因不变。在回肠中，与假手术组动物相比，SBS组中有5个基因下调，6个基因不变。与对照动物相比，SBS大鼠的SMO、GIL和PTCH mRNA及蛋白质水平（通过实时PCR和蛋白质印迹法测定）也显著降低了三到四倍。
大鼠大规模肠切除术后两周，细胞更新加速伴随着Hh信号通路的抑制。Hh信号可能是大鼠大规模肠切除术后肠道适应过程中上皮与下层间充质基质之间相互作用的重要调节因子。
