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These processes damage kidney cells, with mesangial cells (MCs) undergoing mesangial expansion. Antihyperglycemic drugs prevent the progression of renal disease. Although tamsulosin is not conventionally used for the treatment of DN, its previously reported anti-fibrotic and anti-inflammatory effects in liver and lung injury models suggest that it may exert renoprotective actions like those of pioglitazone, which has also been shown to improve cellular carbohydrate and lipid metabolism. MCs were exposed to 20 mM glucose medium and treated with either 50 nM tamsulosin or 100 nM pioglitazone. Subsequently, cell proliferation, inflammatory markers (NF-\u03baB, IL-1\u03b2, IL-17), fibrogenic markers (TGF-\u03b2, collagen I), oxidative stress parameters (NRF2, superoxide), and indicators of mesangial activation (\u03b1-SMA, rhodamine\u2013phalloidin) were assessed in vitro. Both treatments reduced cellular proliferation and hypertrophy, attenuated the release of reactive oxygen species (ROS), decreased IL-17 and \u03b1-SMA expression, and reduced mesangial activation and hypertrophy. In an in vivo model of DN in Wistar rats, both treatments decreased mesangial cell activation and expansion. In conclusion, tamsulosin and pioglitazone exert anti-fibrogenic and anti-inflammatory effects in MCs exposed to HG, thereby limiting mesangial activation and expansion.<\/jats:p>","DOI":"10.3390\/ijms26199277","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:54:54Z","timestamp":1758642894000},"page":"9277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Modulation of Mesangial Cells by Tamsulosin and Pioglitazone Under Hyperglycemic Conditions: An In Vitro and In Vivo Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Sandra Lizbeth","family":"Aguilera-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Department of Morphology, Basic Sciences Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-6919","authenticated-orcid":false,"given":"Mart\u00edn Humberto","family":"Mu\u00f1oz-Ortega","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Basic Sciences Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9714-1974","authenticated-orcid":false,"given":"Sandra Luz","family":"Mart\u00ednez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Basic Sciences Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Christopher","family":"Morones-Gamboa","sequence":"additional","affiliation":[{"name":"Department of Morphology, Basic Sciences Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3083-0131","authenticated-orcid":false,"given":"Javier","family":"Ventura-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Morphology, Basic Sciences Center, Universidad Aut\u00f3noma de Aguascalientes, Aguascalientes 20100, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1055\/a-2435-8264","article-title":"Diabetic Nephropathy: Pathogenesis, Mechanisms, and Therapeutic Strategies","volume":"57","author":"Dwivedi","year":"2025","journal-title":"Horm. 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