The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat

• Published in: Pediatric surgery international Vol. 34; no. 2; pp. 217 - 225
• Main Authors: Sukhotnik, I., Shahar, Y. Ben, Pollak, Y., Dorfman, T., Shefer, H. Kreizman, Assi, Z. E., Mor-Vaknin, N., Coran, A. G.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2018; Springer Nature B.V
• Subjects: Apoptosis; Cytoskeleton; Gene expression; Medicine; Medicine & Public Health; Original Article; Pediatric Surgery; Pediatrics; Rodents; Surgery; Vimentin; Cytoskeleton; Short bowel syndrome; Cell turnover; Intermediate filaments; Desmin
• ISSN: 0179-0358; 1437-9813
• DOI: 10.1007/s00383-017-4192-2

Purpose Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS). Materials and 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 (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry. Results 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, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-β, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals). Conclusions Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation.