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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Diabetic kidney disease (DKD) remains a leading cause of chronic kidney disease worldwide despite current standard therapies. c-Kit+ renal progenitor cells have been implicated in kidney repair and regeneration. We investigated whether mesenchymal stem cells (MSCs) and the sodium-glucose cotransporter-2 inhibitor empagliflozin are associated with differential modulation of intrarenal c-Kit+ cell expression in a preclinical model of DKD using BTBRob\/ob mice.Methods:These BTBRob\/ob mice were allocated into three groups: untreated DKD, MSC-treated DKD, and empagliflozin-treated DKD, and were compared with BTBR wild-type (WT) controls. BTBRob\/ob mice received empagliflozin formulated inchow ad libitum at 25 mg\/kg (Jardiance\u00ae, Boehringer Ingelheim, Ingelheim am Rhein, RP, Germany) starting at 4\u20135 weeks of age. MSCs (1 \u00d7 106 cells per dose) were administered intraperitoneally at 8 and 10 weeks of age. Animals were evaluated at 10, 14\u201315, and 18\u201320 weeks. Renal c-Kit gene expression was quantified by quantitative real-time PCR (qPCR), and protein expression was assessed by immunohistochemistry in the cortex, medulla, and glomeruli. Statistical analyses included mixed-effects models and two-way analysis of variance (ANOVA).Results:c-Kit expression was significantly influenced by time and treatment in both cortex and medulla. In the renal cortex, MSC therapy was associated with a transient increase in c-Kit gene expression at 14\u201315 weeks, followed by a reduction at 18\u201320 weeks. Empagliflozin predominantly modulated cortical c-Kit expression at later time points. Immunohistochemistry demonstrated higher cortical c-Kit protein expression in MSC-treated animals compared with untreated DKD mice. In the medulla, MSC-treated mice exhibited increased c-Kit expression at 14\u201315 weeks, which declined at 18\u201320 weeks. Empagliflozin had a modest effect on c-Kit expression and was associated with infrequent glomerular immunoreactivity at 14\u201315 weeks.Conclusions:MSC therapy and empagliflozin are associated with distinct temporal patterns of c-Kit expression in DKD. MSC treatment showed early modulation of c-Kit expression, whereas empagliflozin exhibited more delayed effects. These findings suggest that c-Kit+ cells are dynamically regulated during DKD progression. Given the absence of functional and mechanistic analyses, these results should be considered hypothesis-generating and warrant further investigation.<\/jats:p>","DOI":"10.31083\/fbl51501","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:17:49Z","timestamp":1785413869000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct Temporal Modulation of Mesenchymal Stem Cells and Empagliflozin on Renal c-Kit Cells in Diabetic Kidney Disease"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3343-5004","authenticated-orcid":true,"given":"Gabriela Esteves","family":"de Jesus","sequence":"first","affiliation":[{"name":"School of Medicine, Faculdade Israelita de Ci\u00eancias da Sa\u00fade Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9559-5265","authenticated-orcid":true,"given":"Rosana Maria Cardoso","family":"de Bastos","sequence":"additional","affiliation":[{"name":"Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sociedade Beneficente Israelita Brasileira Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-3569","authenticated-orcid":true,"given":"Christian","family":"S\u00e1vio-Silva","sequence":"additional","affiliation":[{"name":"Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sociedade Beneficente Israelita Brasileira Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-1644","authenticated-orcid":true,"given":"Stephany","family":"Beyerstedt","sequence":"additional","affiliation":[{"name":"Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sociedade Beneficente Israelita Brasileira Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9990-6018","authenticated-orcid":true,"given":"Marcella Liciani","family":"Franco","sequence":"additional","affiliation":[{"name":"Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sociedade Beneficente Israelita Brasileira Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-8380","authenticated-orcid":true,"given":"Samirah Abreu","family":"Gomes","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Internal Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo, SP 05403-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-2484","authenticated-orcid":true,"given":"\u00c9rika Bevilaqua","family":"Rangel","sequence":"additional","affiliation":[{"name":"Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sociedade Beneficente Israelita Brasileira Albert Einstein, S\u00e3o Paulo, SP 05653-000, Brazil"},{"name":"Nephrology Division, Medicine Department, Federal University of S\u00e3o Paulo, S\u00e3o Paulo, SP 04038-031, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Duncan BB, Magliano DJ, Boyko EJ. 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