Partially hydrolyzed guar gum enhances colonic epithelial wound healing via activation of RhoA and ERK1/2.
OBJECTIVE
Healing of the intestinal mucosal epithelium was found to be a critical factor in the treatment of inflammatory bowel disease (IBD). In this study, we provide further evidence that partially hydrolyzed dietary fiber (PHGG) enhances colonic epithelial cell wound healing, and partially characterize the mechanism that governs this process.


METHODS
Young adult mouse colonic (YAMC) epithelial cells were scraped with a 10 μl micro-pipette tip to denude a round of the monolayer and were incubated with PHGG. The area of cell migration was measured using Image J software. Meanwhile, Rho activation assays were utilized to monitor Rho activation levels. To assess in vivo effects, C57B6 mice were treated with DSS for 7 days and then provided food supplemented with PHGG for 8 days.


RESULTS
YAMC cells treated with PHGG exhibited significantly enhanced wound healing compared to the control cells; however, this enhancement was inhibited by both Y-27632 (RhoA inhibitor) and U0126 (ERK1/2 inhibitor). Likewise, there was a PHGG-dependent increase in F-actin accumulation and Rho kinase activity that was blocked by U0126. Meanwhile, PHGG-dependent ERK1/2 activity was not inhibited by Y-27632. In the DSS-induced mouse colitis model, animals that received food supplemented with PHGG exhibited significant recovery of the colonic mucosa.


CONCLUSIONS
In this study, we demonstrate that PHGG promotes colonic epithelial cell wound healing via activation of RhoA, which occurs downstream of ERK1/2 activation. These findings indicate that PHGG could be utilized as a therapeutic agent for patients with intestinal mucosal damage such as those with IBD.
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yusuke
Y
Horii
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Kazuhiko
K
Uchiyama
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yuki
Y
Toyokawa
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yuma
Y
Hotta
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Makoto
M
Tanaka
Nutrition Division, Taiyo Kagaku Co. Ltd, Yokkaichi, Mie, Japan.
Zenta
Z
Yasukawa
Nutrition Division, Taiyo Kagaku Co. Ltd, Yokkaichi, Mie, Japan.
Makoto
M
Tokunaga
Nutrition Division, Taiyo Kagaku Co. Ltd, Yokkaichi, Mie, Japan.
Tsutomu
T
Okubo
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Katsura
K
Mizushima
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yasuki
Y
Higashimura
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Osamu
O
Dohi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Tetsuya
T
Okayama
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Naohisa
N
Yoshida
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Kazuhiro
K
Katada
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Kazuhiro
K
Kamada
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Osamu
O
Handa
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Takeshi
T
Ishikawa
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Tomohisa
T
Takagi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Hideyuki
H
Konishi
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yuji
Y
Naito
Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachidori, Kamigyo-ku, Kyoto 602-8566, Japan. k-uchi@koto.kpu-m.ac.jp.
Yoshito
Y
Itoh
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000188:drug therapy; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005685:Galactans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008351:Mannans / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053149:Plant Gums / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein
D005685:Galactans; D008351:Mannans; D053149:Plant Gums; C007894:guar gum; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein