The Journal of Practical Medicine >
The role of PTTG1 in colonic inflammation by regulating intestinal epithelial cells pyroptosis
Received date: 2023-10-23
Online published: 2024-03-26
Objective To investigate whether the pituitary tumor transformation gene 1 （PTTG 1） plays a role in colitis by regulating intestinal epithelial cells pyroptosis. Methods Ten PTTG 1 wild?type （WT） mice and Ten PTTG 1 knockout （KO） mice were randomly divided into 4 groups of 5 each， respectively PTTG1 WT control and experimental group， PTTG1 KO control and experimental group. The mice in the experimental group were given 3% dextran sodium sulfate （DSS） for 6 days to induce acute colitis， and the control group was given sterile double distilled water（ddH2O）. The disease activity index of the respective group of mice was observed and recorded. Mouse colonic tissue were collected， and the expression levels of NLRP3， ASC， and GSDMD were determined by immunohistochemistry and western blot. In HCoEpiC， PTTG1 expression was knocked down using shRNA， and the cells were subsequently treated with TNF?α to induce inflammation. Then， the expression of GSDMD was detected. Results The expression of PTTG1 was decreased in colonic mucosal tissue in mice with acute colitis（P < 0.01）. Compared with WT mice， the colitis was significantly aggravated in PTTG1 KO mice after 3% DSS treatment. The expression of pyroptosis?related proteins was significantly up?regulated in the colon mucosal tissues of PTTG1 KO experimental mice（P < 0.05）. After knocking down the expression of PTTG1 in HCoEpiC and TNF?α treatment， the expression levels of GSDMD were significantly up?regulated（P < 0.05）. Conclusion PTTG1 reduced pyroptosis in intestinal epithelial cells （IECs）， while PTTG1 loss can enhance IEC pyroptosis， aggravating colonic inflammation.
Key words： ulcerative colitis; PTTG1; pyroptosis; GSDMD
Yujun YI , Xiaoming ZHAI , Huiling LIU , Jin. TAO . The role of PTTG1 in colonic inflammation by regulating intestinal epithelial cells pyroptosis[J]. The Journal of Practical Medicine, 2024 , 40(5) : 632 -638 . DOI: 10.3969/j.issn.1006-5725.2024.05.008
| 1 | LE BERRE C， HONAP S， PEYRIN-BIROULET L. Ulcerative colitis ［J］. Lancet， 2023， 402（10401）： 571-584. doi:10.1016/s0140-6736(23)00966-2 |
| 2 | CHEN K， SHANG S， YU S， et al. Identification and exploration of pharmacological pyroptosis-related biomarkers of ulcerative colitis ［J］. Front Immunol， 2022， 13： 998470. doi:10.3389/fimmu.2022.998470 |
| 3 | VANAJA S K， RATHINAM V A， FITZGERALD K A. Mechanisms of inflammasome activation： recent advances and novel insights ［J］. Trend Cell biol， 2015， 25（5）： 308-315. doi:10.1016/j.tcb.2014.12.009 |
| 4 | WU C， LU W， ZHANG Y， et al. Inflammasome Activation Triggers Blood Clotting and Host Death through Pyroptosis ［J］. Immunity， 2019， 50（6）： 1401-1411.e4. doi:10.1016/j.immuni.2019.04.003 |
| 5 | 易莎，胡楠，李粤，等. 过氧化物酶体增殖物激活受体-γ对P. acnes诱导的人角质形成细胞焦亡、增殖及凋亡的影响［J］.实用医学杂志， 2023， 39（16）： 2043-2049. |
| 6 | ZENG B， HUANG Y， CHEN S， et al. Dextran sodium sulfate potentiates NLRP3 inflammasome activation by modulating the KCa3.1 potassium channel in a mouse model of colitis ［J］. Cell Mol Immunol， 2022， 19（8）： 925-943. doi:10.1038/s41423-022-00891-0 |
| 7 | HEANEY A P， SINGSON R， MCCABE C J， et al. Expression of pituitary-tumour transforming gene in colorectal tumours ［J］. Lancet， 2000， 355（9205）： 716-719. doi:10.1016/s0140-6736(99)10238-1 |
| 8 | LAI Y， XIN D， BAI J， et al. The important anti-apoptotic role and its regulation mechanism of PTTG1 in UV-induced apoptosis ［J］. J Biochem Molecul Biol， 2007， 40（6）： 966-972. doi:10.5483/bmbrep.2007.40.6.966 |
| 9 | TIEN S， ZHOU H， ZHOU Q， et al. PTTG1 alleviates acute alcoholic liver injury by inhibiting endoplasmic reticulum stress-induced hepatocyte pyroptosis ［J］. Liver Int， 2023， 43（4）： 840-854. doi:10.1111/liv.15535 |
| 10 | KOBAYASHI T， SIEGMUND B， LE BERRE C， et al. Ulcerative colitis ［J］. Nature Rev Dis Primers， 2020， 6（1）： 74. doi:10.1038/s41572-020-0205-x |
| 11 | LARABI A， BARNICH N， NGUYEN H T T. New insights into the interplay between autophagy， gut microbiota and inflammatory responses in IBD ［J］. Autophagy， 2020， 16（1）： 38-51. doi:10.1080/15548627.2019.1635384 |
| 12 | ZENG L X， TAO J， LIU H L， et al. β-Arrestin2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis ［J］. Mucos Immunol， 2015， 8（3）： 683-695. doi:10.1038/mi.2014.104 |
| 13 | XU M， TAO J， YANG Y， et al. Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis ［J］. Cell Death Dis， 2020， 11（2）： 86. doi:10.1038/s41419-020-2299-1 |
| 14 | SLAUFOVA M， KARAKAYA T， DI FILIPPO M， et al. The gasdermins： a pore-forming protein family expressed in the epidermis ［J］. Front Immunol， 2023， 14： 1254150. doi:10.3389/fimmu.2023.1254150 |
| 15 | ZHANG S， LIANG Y， YAO J， et al. Role of Pyroptosis in Inflammatory Bowel Disease （IBD）： From Gasdermins to DAMPs ［J］. Front Pharmacol， 2022， 13： 833588. doi:10.3389/fphar.2022.833588 |
| 16 | 张洪江，李树霞，翁洪亮. miR-223调控NLRP3/Caspase-1通路在氯胺酮诱导发育期大鼠海马神经元焦亡中的作用［J］.实用医学杂志， 2022， 38（7）： 848-852. doi:10.3969/j.issn.1006-5725.2022.07.013 |
| 17 | 汪乐新，刘超，马天龙，等. LncRNA H19调控肾小球足细胞焦亡中作用［J］.实用医学杂志， 2023， 39（1）： 12-20. |
| 18 | BULEK K， ZHAO J， LIAO Y， et al. Epithelial-derived gasdermin D mediates nonlytic IL-1β release during experimental colitis ［J］. J Clin Investig， 2020， 130（8）： 4218-4234. |
| 19 | PRIVITERA G， RANA N， ARMUZZI A， et al. The gasdermin protein family： emerging roles in gastrointestinal health and disease ［J］. Nature Rev Gastroenterol Hepatol， 2023， 20（6）： 366-387. doi:10.1038/s41575-023-00743-w |
| 20 | CHEN W S， YU Y C， LEE Y J， et al. Depletion of securin induces senescence after irradiation and enhances radiosensitivity in human cancer cells regardless of functional p53 expression ［J］. Int J Radiat Oncol Biol Physic， 2010， 77（2）： 566-574. doi:10.1016/j.ijrobp.2009.12.013 |
/
| 〈 |
|
〉 |