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Stratified layer analysis reveals intrinsic leptin stimulates cryptal mesenchymal cells for controlling mucosal inflammation.

Abstract
Mesenchymal cells in the crypt play indispensable roles in the maintenance of intestinal epithelial homeostasis through their contribution to the preservation of stem cells. However, the acquisition properties of the production of stem cell niche factors by the mesenchymal cells have not been well elucidated, due to technical limitations regarding the isolation and subsequent molecular and cellular analyses of cryptal mesenchymal cells. To evaluate the function of mesenchymal cells located at the large intestinal crypt, we established a novel method through which cells are harvested according to the histologic layers of mouse colon, and we compared cellular properties between microenvironmental niches, the luminal mucosa and crypts. The gene expression pattern in the cryptal mesenchymal cells showed that receptors of the hormone/cytokine leptin were highly expressed, and we found a decrease in Wnt2b expression under conditions of leptin receptor deficiency, which also induced a delay in cryptal epithelial proliferation. Our novel stratified layer isolation strategies thus revealed new microenvironmental characteristics of colonic mesenchymal cells, including the intrinsic involvement of leptin in the control of mucosal homeostasis.
AuthorsSeiichi Matsumura, Yosuke Kurashima, Sayuri Murasaki, Masako Morimoto, Fujimi Arai, Yukari Saito, Nana Katayama, Dayoung Kim, Yutaka Inagaki, Takahiro Kudo, Peter B Ernst, Toshiaki Shimizu, Hiroshi Kiyono
JournalScientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 18351 (10 27 2020) ISSN: 2045-2322 [Electronic] England
PMID33110098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Leptin
  • Receptors, Leptin
  • Wnt Proteins
  • Wnt2b protein, mouse
  • leptin receptor, mouse
Topics
  • Animals
  • Cellular Microenvironment
  • Colon (metabolism)
  • Homeostasis
  • Inflammation (metabolism)
  • Intestinal Mucosa (cytology, metabolism)
  • Leptin (metabolism)
  • Male
  • Mesenchymal Stem Cells (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Leptin (metabolism)
  • Transcriptome
  • Wnt Proteins (metabolism)

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