{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:08:40Z","timestamp":1773994120197,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003069","name":"Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"crossref","award":["SIP-20253840"],"award-info":[{"award-number":["SIP-20253840"]}],"id":[{"id":"10.13039\/501100003069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["CF-2023-I-1131"],"award-info":[{"award-number":["CF-2023-I-1131"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia\u2013reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36\u03b1 in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol\/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36\u03b1. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy.<\/jats:p>","DOI":"10.3390\/ijms27062751","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:10:04Z","timestamp":1773825004000},"page":"2751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesangial Cells (MES-SV40) Cultured in High Glucose Produce IL-36\u03b1, Which Is Associated with Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"27","author":[{"given":"Mar\u00eda Marcela","family":"S\u00e1nchez-Torres","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunomicrobiolog\u00eda, Departamento de Microbiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar G.","family":"Pelcastre-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Aplicada, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2143","authenticated-orcid":false,"given":"Fernando","family":"G\u00f3mez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Enfermedades Osteoarticulares e Inmunol\u00f3gicas, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Nacional de Medicina y Homeopat\u00eda del Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isa\u00ed","family":"Mart\u00ednez-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Aplicada, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-1419","authenticated-orcid":false,"given":"Jos\u00e9 Mart\u00edn","family":"Murrieta-Coxca","sequence":"additional","affiliation":[{"name":"Placenta Lab, Department of Obstetrics, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alma Nelly","family":"Diaz-Herreros","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Aplicada, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"},{"name":"Centro de Investigaci\u00f3n Cient\u00edfica Serendipia Asociaci\u00f3n Civil, Tl\u00e1huac, Mexico City 13210, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo W.","family":"Heredia-Murillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Aplicada, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-7010","authenticated-orcid":false,"given":"Juan C.","family":"Cancino-Diaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunomicrobiolog\u00eda, Departamento de Microbiolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario E.","family":"Cancino-Diaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Aplicada, Departamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas del Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1189\/jlb.3RI1014-495R","article-title":"Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions","volume":"97","author":"Gabay","year":"2015","journal-title":"J. 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