Distinct localization of mature hgf from its precursor form in developing and repairing the stomach

Nawaphat Jangphattananont, Hiroki Sato, Ryu Imamura, Katsuya Sakai, Yumi Terakado, Kazuhiro Murakami, Nick Barker, Hiroko Oshima, Masanobu Oshima, Junichi Takagi, Yukinari Kato, Seiji Yano, Kunio Matsumoto

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain HGF (tcHGF) can activate the MET receptor. We investigated the localization of tcHGF and activated/phosphorylated MET (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total HGF (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial cells in endodermal organs, including the stomach. In the adult stomach, total HGF was localized in smooth muscle cells, and tcHGF was mainly localized in the glandular base region. Immunostaining for pMET and Lgr5-driven green fluorescent protein (GFP) indicated that pMET localization overlapped with Lgr5+ gastric stem cells. HGF promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. pMET and tcHGF localizations changed during regeneration following gastric injury. These results indicate that MET is constantly activated in gastric stem cells and that the localization of pMET differs from the primary localization of precursor HGF but has a close relationship to tcHGF. Our results suggest the importance of the microenvironmental generation of tcHGF in the regulation of development, regeneration, and stem cell behavior.

Original languageEnglish
Article number2955
JournalInternational journal of molecular sciences
Volume20
Issue number12
DOIs
Publication statusPublished - 2019 Jun 2

Keywords

  • HGF
  • MET receptor
  • Regeneration
  • Smooth muscle cell
  • Stem cell

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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