Intestinal ischemia/reperfusion (I/R) injury is a common pathophysiological phenomenon widely present in various primary intestinal diseases and systemic critical diseases, which can cause multiorgan dysfunction and failure, and is associated with high morbidity and mortality. Therefore, it is of paramount importance to investigate the mechanisms underlying intestinal inflammation/inflammatory responses and identify potential therapeutic targets.
Recently, the research team of Professor Tian Xiaofeng of Dalian Medical University published a research paper dated April 9, 2026. Chinese medical journal Title: “Growth arrest and DNA damage-induced β (Gad 45B) MST1/Hippo promotes apoptosis in intestinal ischemia/reperfusion via DNA demethylation. ” The study reports: Gad 45B interact with Tet 1 MST1 promotes DNA demethylation and thereby induces MST1 expressed and subsequently activates the Hippo pathway and exacerbates apoptosis after intestinal I/R.
GADD45B is an important stress sensor that mediates various cellular responses and regulates multiple biological processes such as cell survival, DNA demethylation and repair, apoptosis, inflammation, and cell cycle arrest. In previous research, Gad 45B is among the top 20 differentially expressed genes after intestinal I/R injury in humans. Furthermore, previous RNA-seq results showed that; Gad 45B Expression is significantly upregulated in mouse models of intestinal I/R. Therefore, the role of Gad 45B Further investigation is needed in intestinal I/R.
What we found in this research is that Gad 45B Expression was significantly increased in H/R-induced Caco-2 cells and mouse intestinal I/R model. specific knockdown Gad 45B alive and in vitro Cell apoptosis was reduced and intestinal and distant organ damage was reduced. in vitro overexpression of Gad 45B H/R-induced intestinal damage and cell apoptosis in Caco-2 cells is exacerbated. These findings suggest that Gad 45B is an important target contributing to cell apoptosis following intestinal injury and intestinal inflammation. Transcriptome KEGG enrichment analysis subsequently identified the Hippo pathway as a downstream target pathway. Gad 45B We conducted studies in intestinal I/R injury and identified its downstream target protein, mammalian sterile 20-like kinase 1 (MST1). If we examine the mechanism in more detail, Gad 45B Regulates the Hippo pathway, which the authors knocked down and overexpressed Gad 45B In Caco-2 cells. Using methylation-specific PCR (MSP) and chromatin immunoprecipitation (ChIP) assays, they found that: Gad 45B provoke MST1 Expression by DNA demethylation. TET enzymes are a type of general demethylase that reduce the level of DNA methylation at gene promoters, thereby stimulating the expression of specific genes. In previous research, Gad 45B It can bind to TET1 and directly mediate region-specific demethylation. To further investigate the molecular basis Gad 45BThe authors first confirmed that MST1 mediated DNA demethylation. Tet 1 Expression was significantly upregulated after intestinal I/R, consistent with the observed trend of GADD45B. Subsequently, ChIP, Co-IP, and MSP assays further confirmed the following: Gad 45B MST1 promotes DNA demethylation through physical interaction with MST1. Tet 1.
In summary, this study demonstrates a proapoptotic role. Gad 45B We investigate its downstream pathways and targets in intestinal I/R and further confirm the important role of epigenetics in intestinal I/R. Mechanically, Gad 45B It interacts with TET1 to promote demethylation of MST1 DNA, thereby activating the Hippo pathway and aggravating intestinal I/R injury. These findings suggest that Gad 45B is an important regulator in intestinal I/R injury, and targeting the GADD45B/TET1/MST1 axis may be a viable therapeutic strategy.
sauce:
Dalian Medical University
Reference magazines:
Yang, F. Others. (2026). GADD45B promotes apoptosis in intestinal ischemia/reperfusion via DNA demethylation of MST1/Hippo. Chinese medical journal. DOI: 10.1097/CM9.0000000000004050. https://journals.lww.com/cmj/fulltext/9900/gadd45b_promotes_apoptosis_in_intestinal.2014.aspx
