Bmp signaling in colonic mesenchyme regulates stromal microenvironment and protects from polyposis initiation

International Journal of Cancer. Journal International Du Cancer
Joannie M AllaireNathalie Perreault

Abstract

In the colon, myofibroblasts are primary contributors in the establishment of the microenvironment involved in tissue homeostasis. Alterations in myofibroblast functions lead to changes resulting in a toxic microenvironment nurturing tumorigenesis. Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in adult gut homeostasis. Studies in genetically-modified mice have shown that Bmp disruption in all cell layers leads to the development of gut polyposis. In contrast, our studies showed that loss of Bmp exclusively in the gastrointestinal epithelium resulted in increased epithelial proliferation without polyposis initiation, thus suggesting a key role for mesenchymal Bmp signaling in polyposis initiation. In order to identify the role of mesenchymal Bmp signaling on the microenvironment and its impact on colonic mucosa, a mouse model was generated with suppression of Bmp signaling exclusively in myofibroblasts (Bmpr1aΔMES). Bmpr1aΔMES mice exhibited increased subepithelial proliferation with changes in cellular composition leading to the development of a primed stroma with modulation of extracellular matrix proteins, immune cells and cytokines as early as 90 days of age. This microenvironmental deregulation w...Continue Reading

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Citations

Feb 15, 2018·International Journal of Molecular Sciences·Xiaofei GuoMingxing Chu
Oct 17, 2019·Annual Review of Physiology·Yongchun Zhang, Jianwen Que
Jul 11, 2018·Journal of Translational Medicine·Andrew J PellattMartha L Slattery
Aug 23, 2018·Frontiers in Oncology·Jeffrey A Rappaport, Scott A Waldman
Jun 2, 2018·Science China. Life Sciences·Shan Wang, Ye-Guang Chen
May 31, 2019·Cellular and Molecular Gastroenterology and Hepatology·Marie-Josée LangloisNathalie Perreault
May 4, 2021·Gastroenterology·Nancy R GoughLopa Mishra

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