Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

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BackgroundGinkgetin aglycone (GA), a novel Ginkgo biloba extract (GBE) by acid hydrolysis and recrystallization, is characterized by higher liposolubility and antioxidation than classical GBEs. There is no study depicting the functional role of GA in acute kidney injury (AKI). Here, we firstly reported the protective effect of GA on lipopolysaccharide (LPS)-induced AKI and its underlying mechanism.MethodsELISA analysis was applied to measure plasma level of TNF-α and IL-6, and NF-κB activity in kidney homogenate. Renal function analysis was performed by detecting serum concentration of Kim-1 and urine level of BUN. Cell apoptosis in kidney tissues was detected by TUNEL assay and caspase-3 activity assay. qRT-PCR was conducted to determine mRNA expression of TNF-α, IL-6 and IκBα. Western blot was carried out to confirm expression of p-IκBα, SIRT1, and iNOS.ResultsGA administration protected mice from LPS-induced AKI by attenuating inflammatory response, renal injury, as well as tubular apoptosis both in vivo. GA suppressed inflammatory response induced by LPS in HK-2 cells. Moreover, GA upregulated SIRT1 expression and blocked the NF-κB signaling pathway in LPS-induced AKT in vivo and vitro. Furthermore, suppression of SIRT1 abated the inhibitory effect of GA on LPS-induced inflammatory response and renal injury.ConclusionsGA prevented LPS-induced AKI by activating SIRT1 via inhibiting the NF-κB signaling pathway, providing new insights into the function and molecular mechanism of GA in AKI. Therefore, GA may be a promising therapeutic agent for the treatment of septic AKI.

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