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

Abstract

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.