Inhibition of miR-17~92 Cluster Ameliorates High Glucose-Induced Podocyte Damage

Abstract

The loss and damage of podocytes is an early feature of diabetic nephropathy (DN). The miR-17∼92 cluster was dysregulated in diabetic and polycystic kidney disease patients, but its role in DN is unclear. Hence, an in vitro study on the high glucose- (HG-) treated mouse podocytes (MPC5) was designed to elucidate the effect of miR-17∼92 cluster downregulation on cell viability, apoptosis, inflammation, fibrosis, and podocyte function. The results suggested that the miR-17∼92 cluster members miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a were upregulated in the renal biopsy tissue of DN patients and HG-treated MPC5. The downregulation of the miR-17∼92 cluster effectively suppressed the cell apoptosis, inflammation, fibrosis, and podocyte dysfunction in HG-stimulated MPC5 cells. The bioinformatics analysis and rescue experiments showed that ABCA1 (ATP-binding cassette transporter A1) is an effector of the miR-17~92 cluster. Silence of ABCA1 inhibited the protective effect of the miR-17∼92 cluster downregulation on podocyte damage. In summary, this research indicated that the downregulation of the miR-17∼92 cluster ameliorates HG-induced podocyte damage via targeting ABCA1.

Long non‐coding RNA H19 promotes myoblast fibrogenesis via regulating the miR‐20a‐5p‐Tgfbr2 axis

“…After that, we established that lnc‐H19/miR‐20a levels were correlated with TGFβ/Smad pathway activity (Figure 5D). The anti‐fibrotic effect of miR‐20a was reported in pulmonary, 38 cardiac, 39 and kidney 40 fibrosis. In this study, artificially up‐regulated and down‐regulated miR‐20a could, respectively, inhibit and promote the levels of fibrotic and mesenchymal markers (Figure 4A,B), suggesting that miR‐20a might be an inhibitor for skeletal muscle fibrosis.…”

MiR‐17‐5p downregulation alleviates apoptosis and fibrosis in high glucose‐induced human mesangial cells through inactivation of Wnt/β‐catenin signaling by targeting KIF23

“…Previous reports suggested that miR-17-5p is highly expressed in the renal biopsy tissues of patients with DN patients as well as in high glucose-treated mouse podocytes, 18 and upregulated miR-17-5p significantly accelerates cell apoptosis in podocytes treated with high glucose. 31 However, the role of miR-17-5p in high glucose-treated MCs is yet unknown.…”

“…MiR-17-5p is a member of the miR-17~92 cluster that was shown to be highly expressed in the renal biopsy tissues of patients with DN patients as well as in high glucose-treated mouse podocytes. 18 Previous study indicated that the occurrence of gestational diabetes is related to increased expression of miR-17-5p. 19 Additionally, miR-17-5p was reported to be responsible for insulin sensitivity and glucose homeostasis.…”

Triptolide inhibits oxidative stress and inflammation via the microRNA-155-5p/brain-derived neurotrophic factor to reduce podocyte injury in mice with diabetic nephropathy

“…According to the literature [ 26 ], after the recovery, passage, and differentiation of MPC5 cells, the cells were grouped as follows: (1) NG group (Normal glucose), MPC5 cells were cultured in RPMI 1640 medium supplemented with 5.5 mM glucose for 48 h; (2) HG group, MPC5 cells were cultured with 25 mM glucose in RPMI 1640 medium for 48 h, and the concentration of HG was determined as per the reference [ 27 ]; (3) HG + TP group, MPC5 cells were cultured with 25 mM glucose and 10 uM TP in RPMI 1640 medium for 48 h, and the administration method and dosage of TP were referred to a previous study [ 10 ]. (4) HG + IRB group, MPC5 cells were cultured in RPMI 1640 medium supplemented with 25 mM glucose and 10 uM irbesartan for 48 h, with irbesartan used as a positive control.…”