Id1 Expression in Endothelial Cells of the Colon Is Required for Normal Response to Injury

Abstract

Inhibitor of DNA binding (ID)-1 is important for angiogenesis during embryogenesis and tumor development. Whether ID1 expression in endothelial cells of the colon is required for normal response to injury is unknown. We demonstrate that Id1 is up-regulated in colonic endothelial cells in an experimental model of colitis and in the inflamed mucosa of patients with inflammatory bowel disease. Because prostaglandin E 2 and tumor necrosis factor-a are also elevated in colitis, we determined whether these factors could induce ID1 transcription in cultured endothelial cells. Tumor necrosis factor-a stimulated ID1 transcription via early growth response 1 protein (Egr-1). By contrast, the induction of ID1 by prostaglandin E 2 was mediated by cAMP response elementebinding protein (CREB). To determine whether the increased ID1 levels in the endothelial cells of inflamed mucosa were an adaptive response that modulated the severity of tissue injury, Id1 was conditionally depleted in the endothelium of mice, which sensitized the mice to more severe chemical colitis, including more severe diarrhea, bleeding, and histological injury, and shorter colon compared with control mice. Moreover, depletion of Id1 in the vasculature was associated with increased CD31 þ aggregates and increased vascular permeability in inflamed mucosa compared with those in Id1 wild-type control mice. These results suggest that endothelial ID1 up-regulation in inflamed colonic mucosa is an adaptive response that modulates the severity of tissue injury. (Am J Pathol 2015 http://dx

Alpha-1-antitrypsin functions as a protective factor in preeclampsia through activating Smad2 and inhibitor of DNA binding 4

“…Prostaglandin can enhance the expression of Smad1/5 phosphorylation and Id1 induced by BMP, and its mechanism is related to inhibitory Smad6. In addition, prostacyclin can inhibit the proliferation of smooth muscle cells, thereby preventing the progression of pulmonary hypertension and increase Smad1/5 phosphorylation and Id1 expression [ 8 ]. In the inflammatory response, the expression of Id1 in endothelial cells will increase in adaptive expression.…”

Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration

“…In summary, these studies suggest that regulating Id gene expression in ECs may be therapeutically relevant to promote EC proliferation and re-endothelialization following vascular injury. For example, loss of Id genes in adult ECs in mice with chemical colitis exacerbates disease resulting in reduced overall survival, indicating that Id genes reduce epithelial tissue injury in this model (Zhang et al, 2015). Thus, inducing Id gene expression with BMPs and FGFs may provide a therapeutic benefit for the treatment of severe colitis and other vascular injuryrelated diseases, including myeloablative stress and smallvessel vasculitis.…”

Primaquine Diphosphate, a Known Antimalarial Drug, Blocks Vascular Leakage Acting Through Junction Stabilization

“…In addition, inhibition of USP1 has the potential to target a variety of cancers (Sacco et al, 2010;Chen et al, 2011;Ma et al, 2019). According to recent studies, USP1 contributes to deubiquitination and stabilization of the differentiation inhibitory proteins of the DNA binding inhibitor (ID) family, and ID1 is known to be associated with permeability (Zhang et al, 2015;Lee et al, 2016;Gadomski et al, 2020). As the expression of ID1 regulates E-cadherin expression (Li et al, 2007), USP1 is likely to contribute the stabilization of adherens junction protein via ID1 in endothelial cells.…”