The role of the BMP signaling cascade in regulation of stem cell activity following massive small bowel resection in a rat.
OBJECTIVE
Bone morphogenetic proteins (BMPs) are a group of growth factors that are implicated in intestinal growth, morphogenesis, differentiation, and homeostasis. The role of the BMP signaling cascade in stimulation of cell proliferation after massive small bowel resection is unknown. The purpose of this study was to evaluate the role of BMP signaling during intestinal adaptation in a rat model of short bowel syndrome (SBS).


METHODS
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 BMP signaling gene expression profiling. BMP-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry.


RESULTS
From the total number of 20,000 probes, 8 genes related to BMP signaling were investigated. From these genes, five genes were found to be up-regulated in jejunum (BMP1-10 %, BMP2-twofold increase, BMP3-10 %, BMP2R-12 % and STAT3-28 %) and four genes to be up-regulated in ileum (BMP1-16 %, BMP2-27 %, BMP3-10 %, and STAT3-20 %) in SBS vs sham animals with a relative change in gene expression level of 10 % or more. SBS rats also demonstrated a significant increase in BMP2 and STAT3 mRNA and protein levels (determined by real-time PCR and Western blot) compared to control animals.


CONCLUSIONS
Two weeks following massive bowel resection in rats, the BMP signaling pathway is stimulated. BMP 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.
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net.|Department of Pediatric Surgery, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048, Haifa, Israel. igor-dr@internet-zahav.net.
I
I
Sukhotnik
Department of Gastroenterology, Bnai Zion Medical Center, Haifa, Israel.
D
D
Berkowitz
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
T
T
Dorfman
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Department of Surgery and Emergency Room, Carmel Medical Center, Haifa, Israel.
Salim
S
Halabi
Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Y
Y
Pollak
Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
J
J
Bejar
Department of Surgery and Emergency Room, Carmel Medical Center, Haifa, Israel.
A
A
Bitterman
Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, MI, USA.
A G
AG
Coran
D000818:Animals; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D007421:Intestine, Small / Q000378:metabolism / Q000601:surgery; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000601:surgery*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins
Bone morphogenetic protein signaling; Bowel resection; Cell proliferation; Short bowel syndrome; Stem cell