Mesenchymal Stem Cells Restore Endothelial Integrity and Alleviate Emotional Impairments in a Diabetic Mouse Model via Inhibition of MMP-9 Activity DOI Open Access

Aoying Chen,

Yuhan Duan,

Shaocong Zhou

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3355 - 3355

Опубликована: Апрель 3, 2025

Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence highlighted a bidirectional relationship between diabetes and depression, with blood-brain barrier (BBB) disruption playing pivotal role in the pathogenesis of therapeutic approaches to both disorders. Mesenchymal stem cells (MSCs) have emerged as promising cell-based strategy for DM; however, their potential mitigate DM-associated emotional deficits remains unclear. This study investigates whether MSCs can restore BBB integrity improve diabetic mouse model via matrix metalloprotein-9 (MMP-9) inhibition. We used biochemical, molecular, behavioral analyses assess function, inflammation, behavior. Our results demonstrated that conditions induce dysfunction, characterized by MMP-9-mediated degradation tight junction (TJ) proteins claudin-5 (Cldn5) occludin (Ocln), alongside neuroinflammation impairments. Notably, MSC administration restored attenuated suppressing MMP-9 activity upregulating TJ proteins. Importantly, treatment not only alleviated anxiety- depressive-like behaviors but also enhanced glycemic control DMmodels. These findings elucidate mechanistic basis therapy DM-related neuropsychiatric complications and, crucially, reveal its dual efficacy concurrently ameliorating symptoms metabolic dysfunction DM models. synergistic effect provides translational rationale advancing MSC-based therapies into clinical applications.

Язык: Английский

Mesenchymal Stem Cells Restore Endothelial Integrity and Alleviate Emotional Impairments in a Diabetic Mouse Model via Inhibition of MMP-9 Activity DOI Open Access

Aoying Chen,

Yuhan Duan,

Shaocong Zhou

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3355 - 3355

Опубликована: Апрель 3, 2025

Diabetes mellitus (DM) has reached pandemic prevalence, significantly impacting global health. Accumulating evidence highlighted a bidirectional relationship between diabetes and depression, with blood-brain barrier (BBB) disruption playing pivotal role in the pathogenesis of therapeutic approaches to both disorders. Mesenchymal stem cells (MSCs) have emerged as promising cell-based strategy for DM; however, their potential mitigate DM-associated emotional deficits remains unclear. This study investigates whether MSCs can restore BBB integrity improve diabetic mouse model via matrix metalloprotein-9 (MMP-9) inhibition. We used biochemical, molecular, behavioral analyses assess function, inflammation, behavior. Our results demonstrated that conditions induce dysfunction, characterized by MMP-9-mediated degradation tight junction (TJ) proteins claudin-5 (Cldn5) occludin (Ocln), alongside neuroinflammation impairments. Notably, MSC administration restored attenuated suppressing MMP-9 activity upregulating TJ proteins. Importantly, treatment not only alleviated anxiety- depressive-like behaviors but also enhanced glycemic control DMmodels. These findings elucidate mechanistic basis therapy DM-related neuropsychiatric complications and, crucially, reveal its dual efficacy concurrently ameliorating symptoms metabolic dysfunction DM models. synergistic effect provides translational rationale advancing MSC-based therapies into clinical applications.

Язык: Английский

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