Claire B Cummins1, Yanping Gu2, Xiaofu Wang1, You-Min Lin3, Xuan-Zheng Shi3, Ravi S Radhakrishnan4,5. 1. Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. 2. Department of Neuroscience, University of Texas Medical Branch, Galveston, TX, USA. 3. Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. 4. Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. rsradhak@utmb.edu. 5. Departments of Pediatrics and Surgery, 301 University Blvd., Galveston, TX, 77555-0353, USA. rsradhak@utmb.edu.
Abstract
INTRODUCTION: Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown. METHODS: Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis. RESULTS: Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-β signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-β signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats' ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues. CONCLUSION: Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.
INTRODUCTION: Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown. METHODS: Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure. Gastric emptying, gastric antrum contractility ileal smooth muscle contractility, and colonic contractility were measured. Muscularis externa was isolated from the ileal segment to prepare smooth muscle protein extracts for Western blot analysis. RESULTS: Compared with sham controls, the baseline rhythmic contractile activities of the antral, ileal, and colonic smooth muscle strips were impaired in the burned rats. Simultaneously, our data showed that ileal muscularis ECM proteins fibronectin and laminin were significantly up-regulated in burned rats compared with sham rats. TGF-β signaling is an important stimulating factor for ECM protein expression. Our results revealed that TGF-β signaling was activated in the ileal muscle of burned rats evidenced by the activation of Smad2/3 expression and phosphorylation. In addition, the total and phosphorylated AKT, which is an important downstream factor of ECM signaling in smooth muscle cells, was also up-regulated in burned rats' ileal muscle. Notably, these changes were not seen in the colonic or gastric tissues. CONCLUSION: Deposition of fibrosis-related proteins after severe burn is contributors to decreased small intestinal motility.
Authors: U D Sohn; W Cao; D C Tang; J T Stull; J R Haeberle; C L Wang; K M Harnett; J Behar; P Biancani Journal: Am J Physiol Gastrointest Liver Physiol Date: 2001-08 Impact factor: 4.052
Authors: Hermes M Oliveira; Hanaa S Sallam; Jonathan Espana-Tenorio; David Chinkes; Dai H Chung; Jiande D Z Chen; David N Herndon Journal: Burns Date: 2009-05-22 Impact factor: 2.744
Authors: You-Min Lin; Yu Fu; John Winston; Ravi Radhakrishnan; Sushil K Sarna; Li-Yen M Huang; Xuan-Zheng Shi Journal: Pain Date: 2017-04 Impact factor: 7.926