Abstract:Objective: To investigate the effects of atractylenolide I (Atr-I) on intestinal barrier dysfunction and Yes-associated protein (YAP)/transcription coactivator containing PDZ binding motif (TAZ) signaling pathway in rats with ulcerative colitis (UC).Methods: UC rat model was constructed,all experimental rats were divided into UC group,17.5,35.0 mg/kg Atr-I dose group (Atr-I-L,Atr-I-H group),35.0 mg/kg Atr-I+17.5 mg/kg Yap inhibitor vitipofin group (Atr-I-H+VTPF group),18 rats in each group,and 18 rats were taken as control group (Control group).After the experiment,the body weight of mice of each group was measured and the disease activity index (DAI) was calculated after intervention.The length of the colon was measured and the pathological morphology changes of the colojisun in each group were observed by hematoxylin-eosin (HE) staining.Serum interleukin (IL)-1β,IL-17 and interferon-γ (IFN-γ) were detected with enzyme-linked immunosorbent assay (ELISA).The positive expression of intestinal mucosal barrier-related protein band-closing protein 1 (ZO-1) and claudin-1 (Claudin-1) in colon tissue of rats of each group were detected by immunohistochemistry.The protein expression levels of YAP,p-YAP and TAZ in colon tissues were detected by western blotting (Western blot).Results: Compared to Control group,the colonic mucosal epithelial cells in UC group were disordered,the goblet cells were significantly reduced,a large amount of infiltration inflammatory cells were found,and ulcers were formed in some areas,even thickening and adhesion,intestinal deformation,mucosal congestion and edema were obvious,body weight,colon length,ZO-1,Claudin-1 positive expression,p-YAP/YAP,and TAZ expression were significantly decreased,and the DAI score,IL-1β,IL-17,and IFN-γ levels were obviously increased (P<0.05).Compared with UC group,the colonic mucosal epithelial injury of rats in Atr-I-L and Atr-I-H groups was improved,body weight,colon length,positive expression of ZO-1,Claudin-1,p-YAP/YAP and TAZ were significantly increased in turn,and the DAI score,IL-1β,IL-17 and IFN-γ levels were significantly decreased in turn (P<0.05).Compared with Atr-I-H group,the colonic mucosal epithelial injury in Atr-I-H+VTPF group was aggravated,body weight,colon length,ZO-1,Claudin-1 positive expression,p-YAP/YAP,and TAZ expression were significantly decreased,and the DAI score,IL-1β,IL-17,and IFN-γ levels were obviously increased (P<0.05).Conclusion: Atr-I can reduce DAI score,inhibit inflammatory response,improve colonic mucosal epithelial injury,and improve intestinal barrier dysfunction in UC rats,the mechanism may be related to the activation of YAP/TAZ signaling pathway.
李森, 田利晖, 韩涛, 闫玲新, 王素梅, 李宏坤. 基于YAP/TAZ信号通路探讨白术内酯I对UC大鼠肠屏障功能障碍的影响[J]. 河北医学, 2024, 30(12): 1993-1999.
LI Sen, TIAN Lihui, HAN Tao, et al. Base on YAP/TAZ Signaling Pathway to Investigate the Effect of Atractylenolide I on Intestinal Barrier Dysfunction in UC Rats. HeBei Med, 2024, 30(12): 1993-1999.
[1] Le Berre C,Honap S,Peyrin-Biroulet L.Ulcerative colitis[J].Lancet,2023,402(10401):571-584. [2] Du L,Ha C.Epidemiology and pathogenesis of ulcerative colitis[J].Gastroenterol Clin North Am,2020,49(4):643-654. [3] Qu L,Shi K,Xu J,et al.Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis[J].Phytomedicine,2022,98(1):153945-153957. [4] Zhou R,Wu Q,Wang M,et al.The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration[J].PLoS Biol,2021,19(2):3001122-3001151. [5] Li H,Cao W,Zhang XB,et al.Atractylenolide1 alleviates gastroparesis in diabetic rats by activating the stem cell factor/ckit signaling pathway[J].Mol Med Rep,2021,24(4):691-700. [6] Veenbergen S,Li P,Raatgeep HC,et al.IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+T cells:relevance to inflammatory bowel disease[J].Mucosal Immunol,2019,12(5):1201-1211. [7] Walrath T,Malizia RA,Zhu X,et al.IFN-γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon[J].Am Physiol Gastrointest Liver Physiol,2020,318(3):479-489. [8] Zhang Y,Zhang Y,Zhao Y,et al.Protection against ulcerative colitis and colorectal cancer by evodiamine via antiinflammatory effects[J].Mol Med Rep,2022,25(5):188-201. [9] Kim NY,Pyo JS,Kang DW,et al.Loss of claudin-1 expression induces epithelial-mesenchymal transition through nuclear factor-κB activation in colorectal cancer[J].Pathol Res Pract,2019,215(3):580-585. [10] Cui L,Guan X,Ding W,et al.Scutellaria baicalensis Georgi polysaccharide ameliorates DSS-induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota[J].Int Biol Macromol,2021,166(1):1035-1045.