{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:07:12Z","timestamp":1760386032237,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/NIDDK","award":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"],"award-info":[{"award-number":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"]}]},{"name":"Cancer Prevention and Research Institute of Texas (CPRIT)","award":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"],"award-info":[{"award-number":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"]}]},{"name":"National Institutes of Health\/NCI","award":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"],"award-info":[{"award-number":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"]}]},{"DOI":"10.13039\/100000005","name":"Department of Defense Career Development Award","doi-asserted-by":"publisher","award":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"],"award-info":[{"award-number":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"],"award-info":[{"award-number":["DK007639","DP150074","R01CA175803","W81XWH2010641","RSG-21-027-01-CSM"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cystathionine gamma-lyase (CSE) and TNF-\u03b1 are now recognized as key regulators of intestinal homeostasis, inflammation, and wound healing. In colonic epithelial cells, both molecules have been shown to influence a variety of biological processes, but the specific interactions between intracellular signaling pathways regulated by CSE and TNF-\u03b1 are poorly understood. In the present study, we investigated these interactions in normal colonocytes and an organoid model of the healthy human colon using CSE-specific pharmacological inhibitors and siRNA-mediated transient gene silencing in analytical and functional assays in vitro. We demonstrated that CSE and TNF-\u03b1 mutually regulated each other\u2019s functions in colonic epithelial cells. TNF-\u03b1 treatment stimulated CSE activity within minutes and upregulated CSE expression after 24 h, increasing endogenous CSE-derived H2S production. In turn, CSE activity promoted TNF-\u03b1-induced NF-\u0138B and ERK1\/2 activation but did not affect the p38 MAPK signaling pathway. Inhibition of CSE activity completely abolished the TNF-\u03b1-induced increase in transepithelial permeability and wound healing. Our data suggest that CSE activity may be essential for effective TNF-\u03b1-mediated intestinal injury response. Furthermore, CSE regulation of TNF-\u03b1-controlled intracellular signaling pathways could provide new therapeutic targets in diseases of the colon associated with impaired epithelial wound healing.<\/jats:p>","DOI":"10.3390\/antiox13091067","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T03:45:21Z","timestamp":1725248721000},"page":"1067","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cystathionine Gamma-Lyase Regulates TNF-\u03b1-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids"],"prefix":"10.3390","volume":"13","author":[{"given":"Francisco","family":"Arroyo Almenas","sequence":"first","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor","family":"T\u00f6r\u0151","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Szaniszlo","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2461-1538","authenticated-orcid":false,"given":"Manjit","family":"Maskey","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketan K.","family":"Thanki","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Valley Health System, Las Vegas, NV 89119, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter A.","family":"Koltun","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory S.","family":"Yochum","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA 17033, USA"},{"name":"Department of Biochemistry & Molecular Biology & Surgery, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina V.","family":"Pinchuk","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Pennsylvania State University College of Medicine, Hershey, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Hellmich","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katalin","family":"M\u00f3dis","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.3748\/wjg.v17.i17.2161","article-title":"Wound healing of intestinal epithelial cells","volume":"17","author":"Iizuka","year":"2011","journal-title":"World J. 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