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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 HGtreated 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. K E Y W O R D Sapoptosis, inflammatory response, miR-15b-5p, oxidative stress, Sema3A

C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p < 0.05). There was no significant correlation between CTRP1 and other IRS-1 serine sites (Ser302, Ser307, Ser612, Ser636/639, and Ser789). Collectively, our results suggested that CTRP1 might improve insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

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