PMID- 37017919 OWN - NLM STAT- MEDLINE DCOM- 20230925 LR - 20230925 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 46 IP - 10 DP - 2023 Oct TI - Hsa_circ_0003928 regulates the progression of diabetic nephropathy through miR-136-5p/PAQR3 axis. PG - 2103-2114 LID - 10.1007/s40618-023-02061-z [doi] AB - BACKGROUND: Diabetic nephropathy (DN) is one of the complications of diabetes and has a high mortality, but its specific pathogenesis is not clear. In recent years, researches on the mechanism of circRNAs in DN have been proved a lot, whereas the functional mechanism of circ_0003928 in DN remains open and it must be investigated to value its important role in DN prevention. METHODS: HK-2 cells were treated with high glucose (HG), normal glucose (NG) or Mannitol. Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed to detect cell proliferation. Enzyme-linked immunosorbent assay (ELISA) was applied to analyze malondialdehyde (MDA) and superoxide dismutase 1 (SOD) levels. Flow cytometry and western blot were preformed to measure cell apoptosis. Real-time quantitative PCR (RT-qPCR) was used to test the levels of circ_0003928, miR-136-5p and progestin and adipoQ receptor family member 3 (PAQR3) mRNA. Western blot was executed to detect Bcl2 associated X (Bax), B cell leukemia/lymphoma 2 (Bcl2), smooth muscle (alphaSMA), apolipoprotein (C-IV) and PAQR3 levels. Luciferase reporter assay and RNA pull-down assay were used to analyze the target relationship between miR-136-5p and circ_0003928 or PAQR3. RESULTS: Circ_0003928 and PAQR3 expression were up-regulated, whereas miR-136-5p was decreased in DN serum and HG-induced HK-2 cells. Circ_0003928 knockdown promoted cell proliferation, and inhibit cell apoptosis, oxidative stress, and fibrosis in HK-2 cells under HG condition. MiR-136-5p silencing overturned the protective effects of si-circ_0003928 on HG-induced HK-2 cells. MiR-136-5p was targeted by circ_0003928 and directly targeted PAQR3. Overexpression of PAQR3 counteracted the inhibitory functions of circ_0003928 knockdown or miR-136-5p overexpression on HG-induced HK-2 cell injury. CONCLUSION: Circ_0003928 acted as a sponge of miR-136-5p to up-regulating PAQR3 expression, and then regulate the proliferation, oxidative stress, fibrosis and apoptosis in HG-induced HK-2 cells. CI - (c) 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Zhang, W AU - Zhang W AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. FAU - Zhang, L AU - Zhang L AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. FAU - Dong, Q AU - Dong Q AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. FAU - Wang, X AU - Wang X AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. FAU - Li, Z AU - Li Z AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. FAU - Wang, Q AU - Wang Q AD - Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China. wangqy187@163.com. LA - eng PT - Journal Article DEP - 20230405 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - IY9XDZ35W2 (Glucose) RN - 0 (MicroRNAs) RN - 0 (MIRN136 microRNA, human) SB - IM MH - Humans MH - *Diabetic Nephropathies/genetics MH - Apoptosis MH - Biological Assay MH - Glucose MH - *MicroRNAs/genetics MH - *Diabetes Mellitus OTO - NOTNLM OT - Circ_0003928 OT - Diabetic nephropathy OT - PAQR3 OT - miR-136-5p EDAT- 2023/04/06 06:00 MHDA- 2023/09/25 06:42 CRDT- 2023/04/05 11:21 PHST- 2022/08/19 00:00 [received] PHST- 2023/03/06 00:00 [accepted] PHST- 2023/09/25 06:42 [medline] PHST- 2023/04/06 06:00 [pubmed] PHST- 2023/04/05 11:21 [entrez] AID - 10.1007/s40618-023-02061-z [pii] AID - 10.1007/s40618-023-02061-z [doi] PST - ppublish SO - J Endocrinol Invest. 2023 Oct;46(10):2103-2114. doi: 10.1007/s40618-023-02061-z. Epub 2023 Apr 5.