Research Paper Volume 16, Issue 4 pp 3302—3331

Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation

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Figure 9. ADSC-derived Exos loaded with miR-204 ameliorate the symptoms of DN rats. (A) The expression of miR-204 of rats in each group using qRT-PCR. (BD) The body weights, renal index, and FBG levels of rats in each group. (E) Plasma TC, TG, Scr, BUN, UM, and ACR of rats in each group using an enzymatic colorimetric assay and ELISA. (FH) Histopathological examinations in the kidney tissues of rats in each group using HE, Masson, and PAS staining (scale bar = 20 μm). (I) The expression of fibronectin, collagen IV, α-SMA, and TGF-β1 in the kidney tissues of rats in each group using western blotting. (J) Cell apoptosis in the kidney tissues of rats in each group using a TUNEL assay (scale bar = 20 μm). Rats in the Exo group were treated with 1.6 mg/kg ADSC-derived Exos via caudal vein injection every two days for eight successive weeks. At the same time, rats in the DN + Exo-mimic NC and DN + Exo-miR-204 mimic groups were treated with ADSC-derived Exos loaded with mimic-NC (negative control) or miR-204 mimic, respectively. Rats in the DN group were injected with the same volume of saline. Data were expressed as mean ± standard deviation (n = 6/group). *p < 0.05 and **p < 0.01 vs. DN group; ^p < 0.05 and ^^p < 0.01 vs DN + Exo-mimic NC group; ns indicates no significant differences between groups. Abbreviations: ADSC: adipose-derived stem cell; Exos: exosomes; miR-204: microRNA-204; DN: diabetic nephropathy; qRT-PCR: quantitative real-time polymerase chain reaction; FBG: fasting blood-glucose; TC: total cholesterol, TG: triglyceride; BUN: blood urea nitrogen; Scr: serum creatinine; UM: urinary microalbumin; ACR: albumin to creatinine ratio; ELISA: enzyme-linked immunosorbent assay; HE: hematoxylin-eosin; PAS: periodic acid-Schiff; α-SMA: alpha-smooth muscle actin; TGF-β1: transforming growth factor beta 1; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.