Gadd45β promotes regeneration after injury through TGFβ-dependent restitution in experimental colitis

Abstract

Dysregulated immune responses and impaired function in intestinal epithelial cells contribute to the pathogenesis of inflammatory bowel disease (IBD). Growth arrest and DNA damage-inducible 45 beta (Gadd45β) has been implicated in the pathogenesis of various inflammatory symptoms. However, the role of Gadd45β in IBD is completely unknown. This study aimed to evaluate the role of Gadd45β in IBD. Gadd45β-KO mice exhibited drastically greater susceptibility to dextran sulfate sodium (DSS)-induced colitis and mortality than C57BL/6J mice. Bone marrow transplantation experiments revealed that Gadd45β functions predominantly in the intestinal epithelium and is critical during the recovery phase. Gadd45β regulates the TGF-β signaling pathway in colon tissue and epithelial cells by inhibiting Smurf-mediated degradation of TGF-β receptor type 1 via competitive binding to the N-terminal domain of Smad7. Furthermore, these results indicate that the Gadd45β-regulated TGF-β signaling pathway is involved in wound healing by enhancing epithelial restitution. These results expand the current understanding of the function of Gadd45β and its therapeutic potential in ulcerative colitis.

Ablation of Gadd45β ameliorates the inflammation and renal fibrosis caused by unilateral ureteral obstruction

“…Previously, 14 we found that Gadd45β can regulate TGF signalling pathways in intestinal epithelial cells. To determine whether…”

“…[21][22][23] Recent studies in experimental animals have shown that Gadd45β is involved in the pathogenesis of various diseases. 14,24,25 In the present study, Gadd45β KO mice were used and UUO surgery was carried out to induce early stage CKD. immune cell infiltration and inflammation, and fibrosis was further investigated in mouse kidneys.…”

The potential roles of NAD(P)H:quinone oxidoreductase 1 in the development of diabetic nephropathy and actin polymerization

“…Total RNA from Kidney cortex region was isolated using TRIzol reagent (Thermo Fisher Scientific) according to manufacturer’s instructions 52 . Double-stranded cDNA synthesis was prepared by using the iScript cDNA Synthesis Kit (BioRad, Hercules, CA, USA).…”

“…Kidney tissues (cortex) or cell lysates were homogenized in RIPA (50 mM Tris–HCl, 150 mM NaCl, 1% NP40, 0.5% Na-deoxycholate, and 0.1% SDS) buffer with protease inhibitor cocktail (Roche Applied Science, Penzberg, Germany) 52 . Protein concentration was determined by using the Bradford assay.…”

Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer

“… 25 26 MDSC-derived ROS are the major inducers of the IEC damage, but MDSC-derived transforming growth factor-β (TGF-β) promotes IEC repair. 27 These double effects drive chronic inflammation. Under the colonic inflammatory milieu, MDSCs downregulate the expression of CCAAT/enhancer-binding protein beta (CEBPβ), a critical transcription factor associated with the suppressive function of MDSCs, and secreted increased levels of proinflammatory molecules.…”