Can Tan, Pieter R Norden, Wei Yu, Ting Liu, Naoto Ujiie, Sun Kyong Lee, Xiaocai Yan, Yaryna Dyakiv, Kazushi Aoto, Sagrario Ortega, Isabelle G De Plaen, Venkatesh Sampath, Tsutomu Kume
Intestinal ischemia underlies several clinical conditions and can result in the loss of the intestinal mucosal barrier. Ischemia-induced damage to the intestinal epithelium is repaired by stimulation of intestinal stem cells (ISCs), and paracrine signaling from the vascular niche regulates intestinal regeneration. Here, we identify FOXC1 and FOXC2 as essential regulators of paracrine signaling in intestinal regeneration after ischemia-reperfusion (I/R) injury. Vascular endothelial cell (EC)- and lymphatic EC (LEC)-specific deletions of Foxc1, Foxc2, or both in mice worsen I/R-induced intestinal damage by causing defects in vascular regrowth, expression of chemokine CXCL12 and Wnt activator R-spondin 3 (RSPO3) in blood ECs (BECs) and LECs, respectively, and activation of Wnt signaling in ISCs...
May 8, 2023: EMBO Reports