Nuclear translocation of H2RSP is impaired in regenerating intestinal epithelial cells of murine colitis model

• Published in: Virchows Archiv : an international journal of pathology 2006-03, Vol.448 (3), p.354-360
• Main Authors: NAGANUMA, Seiji, ITOH, Hiroshi, UCHIYAMA, Shuichiro, NAGAIKE, Koki, TANAKA, Hiroyuki, AKIYAMA, Yutaka, CHIJIIWA, Kazuo, KATAOKA, Hiroaki
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cells; Chromosome aberrations; Colitis, Ulcerative - etiology; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Cytoplasm - metabolism; Cytoplasm - pathology; Dextran Sulfate - pharmacology; Disease Models, Animal; Gastrointestinal tract; Gene Expression - drug effects; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Investigative techniques, diagnostic techniques (general aspects); Medical genetics; Medical sciences; Mice; Mice, Inbred C57BL; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proteins; Regeneration - drug effects; Regeneration - physiology; RNA, Messenger - metabolism; Signal Transduction; Sodium sulfate; Transcription Factors - genetics; Transcription Factors - metabolism; Translocation; Translocation, Genetic - drug effects; Up-Regulation
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-005-0064-6

Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a recently identified nuclear peptide that is abundantly expressed in the gastrointestinal tract. In this study, we analyzed the expression of H2RSP in normal and injured intestinal mucosa in a murine experimental colitis induced by oral administration of 2.5% dextran sodium sulfate. Results of immunohistochemistry and in situ hybridization showed that H2RSP was expressed predominantly in the epithelium of normal intestine. Whereas H2RSP was localized in the cytoplasm of cells in the crypt, it was translocated into the nuclei of the surface epithelial cells. In injured intestine, H2RSP was detected in the cytoplasm of regenerating epithelial cells, and the nuclear translocation was impaired even in the surface epithelium. However, the mRNA level was not significantly altered in these cells by real-time reverse transcription-polymerase chain reaction using total RNAs obtained from the fractionated mucosal tissue samples prepared by laser-captured microdissection technique. On the other hand, H2RSP mRNA was significantly upregulated in the stromal cells of injured intestinal mucosa compared with those in normal mucosa, which shows cytoplasmic localization of H2RSP. These circumstantial evidences suggest that the nuclear translocation of H2RSP may be related to a signaling involved in the transition from cellular proliferation to differentiation.