Miwa Satake1, Hirotake Sakuraba2, Hiroto Hiraga1, Shukuko Yoshida1,3, Yui Akemoto4, Shinji Ota1, Yasuhisa Murai1, Keisuke Hasui1, Shogo Kawaguchi5, Hidezumi Kikuchi1, Shinsaku Fukuda1. 1. department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. 2. department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; hirotake@hirosakiu.ac.jp. 3. Shibata Irika Co. Ltd, Hirosaki, Japan. 4. department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. 5. department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Abstract
BACKGROUND/AIM: Transforming growth factor β (TGFβ) signaling plays a key role in modulating intestinal epithelial cell (IEC) homeostasis. The present study aimed to investigate the direct effect of tacrolimus on TGFβ signaling in IECs. MATERIALS AND METHODS: The protective effects of tacrolimus, with or without anti-TGFβ antibody, in dextran sulfate sodium (DSS)-induced colitis were evaluated. RESULTS: Tacrolimus ameliorated IEC apoptosis-mediated mucosal destruction despite anti-TGFβ treatment. TGFβ receptor type II (TGFβ-RII), phosphor-SMAD family members 2/3, and phosphor-extracellular signal-regulated kinase (ERK) expression in IECs was enhanced in tacrolimus-treated mice, and these positive effects were maintained despite anti-TGFβ treatment. Moreover, tacrolimus induced TGFβ-RII up-regulation through ERK activation. CONCLUSION: Our data indicate that tacrolimus directly activated TGFβ-SMAD signaling via the ERK pathway in IECs, thereby providing protection against apoptosis-mediated intestinal epithelial injury.
BACKGROUND/AIM: Transforming growth factor β (TGFβ) signaling plays a key role in modulating intestinal epithelial cell (IEC) homeostasis. The present study aimed to investigate the direct effect of tacrolimus on TGFβ signaling in IECs. MATERIALS AND METHODS: The protective effects of tacrolimus, with or without anti-TGFβ antibody, in dextran sulfate sodium (DSS)-induced colitis were evaluated. RESULTS: Tacrolimus ameliorated IEC apoptosis-mediated mucosal destruction despite anti-TGFβ treatment. TGFβ receptor type II (TGFβ-RII), phosphor-SMAD family members 2/3, and phosphor-extracellular signal-regulated kinase (ERK) expression in IECs was enhanced in tacrolimus-treated mice, and these positive effects were maintained despite anti-TGFβ treatment. Moreover, tacrolimus induced TGFβ-RII up-regulation through ERK activation. CONCLUSION: Our data indicate that tacrolimus directly activated TGFβ-SMAD signaling via the ERK pathway in IECs, thereby providing protection against apoptosis-mediated intestinal epithelial injury.
Authors: Thomas Karrasch; Kris A Steinbrecher; Brigitte Allard; Albert S Baldwin; Christian Jobin Journal: J Cell Physiol Date: 2006-06 Impact factor: 6.384
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