Exosomal Circvma21 Derived From Adipose-Derived Stem Cells Alleviates Sepsis-Induced Acute Kidney Injury by Targeting Mir-16-5p

Abstract

Background Exosome from adipose-derived stem cells (ADSCs-Exo) has been shown to inhibit the progression of human diseases, including sepsis-related acute kidney injury (AKI). CircVMA21 is considered to be an important regulator for sepsis-related AKI. However, whether ADSCs-Exo affected sepsis-induced AKI by delivering circVMA21 is not clear. Methods ADSCs was identified by alizarin red staining, oil red O staining, and flow cytometry. ADSCs-Exo was authenticated by transmission electron microscopy, nanoparticle tracking analysis, western blot analysis, and immunofluorescence assay. Cell apoptosis was assessed by flow cytometry, and inflammation cytokine levels were determined by ELISA. Lactate production was assessed using Lactate Acid Content Assay Kit. The expression levels of aerobic glycolysis-related markers, circVMA21 and miR-16-5p were evaluated by qRT-PCR. Dual-luciferase reporter assay and RIP assay were employed to detect RNA interaction. Animal experiments were used to evaluate the role of ADSCs-Exo on renal function and cell injury in LPS-induced AKI mice model. Results ADSCs-Exo inhibited LPS-induced HK-2 cell apoptosis, inflammation and aerobic glycolysis. Knockdown of exosomal circVMA21 derived from ADSCs enhanced HK-2 cell injury induced by LPS. In terms of mechanism, circVMA21 could serve as sponge for miR-16-5p. Besides, miR-16-5p inhibitor reversed the promotion effect of Exo-sh-circVMA21 on LPS-induced cell injury. In addition, ADSCs-Exo protected LPS-induced AKI in mice by increasing circVMA21 expression and decreasing miR-16-5p expression. Conclusion Exosomal circVMA21 derived by ADSCs relieved LPS-induced AKI through targeting miR-16-5p, which provided a potential molecular target for treating sepsis-related AKI.

Baicalin alleviates oxygen–glucose deprivation/reoxygenation‐induced SK‐N‐SH cell injury via the regulation of miR‐556‐3p/ACSL4 pathway

“…MicroRNA (miRNA) is a noncoding RNA with a size of about 20-25 nt, which plays a regulatory function by interacting with target mRNA (An et al, 2023;Anglicheau et al, 2010;Sacar Demirci et al, 2019;Wang et al, 2023). Abnormal miRNA expression may lead to the occurrence and development of human diseases, including IS (Can et al, 2022;Gugliandolo et al, 2021;He et al, 2023;Vazquez et al, 2023). Many miRNAs have been confirmed to be related to IS process, such as miR-451 (Wang et al, 2021) and miR-641 (Pan et al, 2022).…”

Circusp42 Ameliorates LPS-Induced Human Renal Epithelial Cells in Vitro by Regulating the Mir-182-5p/Dusp1 Axis

“…In addition, upregulated Circ_0001818 in LPS-treated HK2 cells aggravates LPS-induced HK2 cell damage by regulating the miR-136-5p/TXNIP axis (17). CircVMA21 derived from extracellular vesicles derived from adipose-derived stem cells (ADSCs) reduces LPS-induced AKI by targeting miR-16-5p (18). It was known that the downregulation of circUSP42 (hsa_circ_0007823) in triple-negative breast cancer was associated with poor prognosis (19).…”