TGF-β promotes fetal gene expression and cell migration velocity in a wound repair model of untransformed intestinal epithelial cells.

Abstract

The early-phase wound repair response of the intestinal epithelium is characterized by rapid and organized cell migration. This response is regulated by several humoral factors, including TGF-β. However, due to a lack of appropriate models, the precise response of untransformed intestinal epithelial cells (IECs) to those factors is unclear. In this study, we established an in vitro wound repair model of untransformed IECs, based on native type-I collagen. In our system, IECs formed a uniform monolayer in a two-chamber culture insert and displayed a stable wound repair response. Gene expression analysis revealed significant induction of Apoa1, Apoa4, and Wnt4 during the collagen-guided wound repair response. The wound repair response was enhanced significantly by the addition of TGF-β. Surprisingly, addition of TGF-β induced a set of genes, including Slc28a2, Tubb2a, and Cpe, that were expressed preferentially in fetal IECs. Moreover, TGF-β significantly increased the peak velocity of migrating IECs and, conversely, reduced the time required to reach the peak velocity, as confirmed by the motion vector prediction (MVP) method. Our current in vitro system could be employed to assess other humoral factors involved in IEC migration and could contribute to a deeper understanding of the wound repair potentials of untransformed IECs.

• Authors: Sho Anzai, Ami Kawamoto, Sayaka Nagata, Junichi Takahashi, Mao Kawai, Reiko Kuno, Sakurako Kobayashi, Satoshi Watanabe, Kohei Suzuki, Hiromichi Shimizu, Yui Hiraguri, Sayaka Takeoka, Hady Yuki Sugihara, Shiro Yui, Shigeru Oshima, Mamoru Watanabe, Ryuichi Okamoto
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 524 Issue 3 Pg. 533-541 (04 09 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32014254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Transforming Growth Factor beta

Topics

• Animals
• Cell Movement (drug effects, genetics)
• Epithelial Cells (drug effects, metabolism, pathology)
• Fetus (drug effects, metabolism)
• Gene Expression Regulation, Developmental (drug effects)
• Intestines (pathology)
• Mice, Inbred C57BL
• Models, Biological
• Organoids (drug effects, metabolism)
• Transforming Growth Factor beta (pharmacology)
• Up-Regulation (drug effects, genetics)
• Wound Healing (drug effects, genetics)