TY - JOUR
T1 - Burn-Induced Impairment of Ileal Muscle Contractility Is Associated with Increased Extracellular Matrix Components
AU - Cummins, Claire B.
AU - Gu, Yanping
AU - Wang, Xiaofu
AU - Lin, You Min
AU - Shi, Xuan Zheng
AU - Radhakrishnan, Ravi S.
N1 - Publisher Copyright:
© 2019, The Society for Surgery of the Alimentary Tract.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Burns
KW - Gastrointestinal motility
KW - Ileus
KW - Myoctes, smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=85074298069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074298069&partnerID=8YFLogxK
U2 - 10.1007/s11605-019-04400-z
DO - 10.1007/s11605-019-04400-z
M3 - Article
C2 - 31637625
AN - SCOPUS:85074298069
SN - 1091-255X
VL - 24
SP - 188
EP - 197
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 1
ER -