title: Adrenomedullin improves intestinal epithelial barrier function by downregulating myosin light chain phosphorylation in ulcerative colitis rats.
abstract: Adrenomedullin (AM) is a pivotal endogenous vasoactive peptide, which can maintain epithelial barrier function in inflammatory bowel disease. Myosin light chain kinase (MLCK)‑dependent phosphorylated myosin light chain kinase (p‑MLC) is a key regulator of intestinal barrier function. The aim of the present study was to investigate the effect and mechanism of AM on the intestinal epithelial barrier in a rat model of ulcerative colitis (UC) induced by 2,4,6‑trinitro‑benzene‑sulfonic acid (TNBS). A total of 21 male Sprague‑Dawley rats were randomly divided into the following three groups and administered different agents for 7 days: The normal group (water and saline), model group (TNBS and saline) and the AM group (TNBS and AM; 1.0 µg). The weight of rats was recorded every day. Serum tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) levels were detected using ELISA kits. Colon tissue was collected for the assessment of histological alterations. The protein expression of MLCK, p‑MLC and zonula occludens‑1 (ZO‑1) was examined by western blot analysis. Intestinal epithelial tight junctions were examined using transmission electron microscopy. The results demonstrated that in colitis model rats, the expression of TNF‑α, IL‑6, MLCK and p‑MLC significantly increased compared with normal rats. In addition, the expression of ZO‑1 decreased (P<0.05) and intestinal epithelial cell permeability increased. Following AM administration, TNF‑α, IL‑6, MLCK and p‑MLC expression significantly decreased compared with the model rats, the expression of ZO‑1 increased (P<0.05) and intestinal epithelial cell permeability reduced. These data indicate a protective effect of AM on intestinal epithelial barrier dysfunction via suppression of inflammatory cytokines and downregulation of MLCK‑p‑MLC in TNBS‑induced UC. In conclusion, AM/MLCK‑p‑MLC may be an important signaling pathway in the occurrence and development of UC.
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Zaifeng
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zuo
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
mesh_terms: D053607:Adrenomedullin / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018994:Myosin Light Chains / Q000032:analysis* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000032:analysis / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D015850:Interleukin-6; D018994:Myosin Light Chains; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D053607:Adrenomedullin; D009219:Myosin-Light-Chain Kinase