miR-15b-5p ameliorated high glucose-induced podocyte injury through repressing apoptosis, oxidative stress, and inflammatory responses by targeting Sema3A.

Podocyte damage is a hallmark of diabetic nephropathy (DN). Accumulating evidence indicates that microRNAs play important roles in the DN pathogenesis. This study aimed to explore the possible roles and underlying mechanisms of miR-15b-5p on high glucose (HG)-triggered podocyte injury. We observed that miR-15b-5p declined dramatically in a time-dependent manner in podocytes exposed to HG. In addition, miR-15b-5p restored cell proliferation in HG-induced podocytes. Meanwhile, forced expression of miR-15b-5p apparently restrained HG-triggered apoptosis of podocytes, concomitant with downregulated in the proapoptotic protein markers Bax and cleavage caspase-3, and upregulated the antiapoptotic protein Bcl-2. Simultaneously, introduction of miR-15b-5p repressed HG-induced oxidative stress damage in HG-treated podocytes, as evidenced by reduced MDA content, NOX4 expression, and enhanced activities of superoxide dismutase and catalase. Moreover, enforced expression of miR-15b-5p remarkably restrained the HG-stimulated inflammatory response, as reflected by attenuated the level of the cytokines IL-1β, TNF-α, and IL-6. More important, we also identified Sema3A as a direct target of miR-15b-5p. Reverse transcription polymerase chain reaction and western blot subsequently confirmed that miR-15b-5p negatively modulated the level of Sema3A. Mechanically, overexpression of Sema3A impeded the beneficial effects of miR-15b-5p on HG-mediated apoptosis, oxidative stress, and inflammatory response. Altogether, these findings manifested that miR-15b-5p protectively antagonized HG-triggered podocyte damage through relieving HG-induced apoptosis, oxidative stress, and inflammatory process in podocytes by targeting Sema3A, suggesting that miR-15b-5p might be a new therapeutic agent to improve management of DN.

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