Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation

Yuriko Yasuda-Onozawa, Osamu Handa, Yuji Naito, Chihiro Ushiroda, Yosuke Suyama, Yuki Toyokawa, Takaaki Murakami, Tomoyo Yasuda, Tomohiro Ueda, Atsushi Majima, Yuma Hotta, Toshifumi Doi, Makoto Tanaka, Yusuke Horii, Yasuki Higashimura, Katsura Mizushima, Mayuko Morita, Yukiko Uehara, Hideki Horie, Akifumi FukuiOsamu Dohi, Tetsuya Okayama, Naohisa Yoshida, Kazuhiro Kamada, Kazuhiro Katada, Kazuhiko Uchiyama, Takeshi Ishikawa, Tomohisa Takagi, Hideyuki Konishi, Yoshito Itoh

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell-like cells. Using Reb-treated LS174T cells, the level of mucin content was assessed by periodic acid-Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel-forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) pathway in mucin secretion by western blotting. The results suggested that Reb strongly enhanced the positivity of PAS staining in LS174T cells, thereby suggesting increased intracellular mucin production. The PCR results indicated that Reb significantly increased MUC2 mRNA in whole cell lysate of LS174T cells. In order to assess the subsequent secretion of mucin by LS174T, MUC2 protein expression in the supernatant was assessed using the dot blot method and it was demonstrated that Reb significantly increased the secretion of MUC2 in a concentration-dependent manner. The p-Akt was significantly increased by Reb treatment, and an Akt inhibitor specifically suppressed MUC2 secretion. Overall, Reb increased mucin secretion directly via p-Akt. Reb-increased mucin may act as a strong non-specific barrier against pathogenic stimulants in various intestinal diseases.

Original languageEnglish
Pages (from-to)8216-8222
Number of pages7
JournalMolecular Medicine Reports
Volume16
Issue number6
DOIs
Publication statusPublished - 12-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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