Wei Shanshan, Zhang Zhiwen, Yan Lu, Mo Yinjuan, Qiu Xianwen, Mi Xiangbin, Lai Kuan
Department of Dermatology, Zhujiang Hospital, Southern Medical University, China.
Department of Dermatology, Nanfang Hospital, Southern Medical University, China.
Stem Cells Int. 2021 Oct 21;2021:3746335. doi: 10.1155/2021/3746335. eCollection 2021.
Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms.
Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis . B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule.
miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24 h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group.
miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.
狼疮性肾炎是系统性红斑狼疮最常见且最严重的并发症。本研究旨在探讨过表达miR-20a的脂肪来源干细胞（ADSC）移植对小鼠狼疮性肾炎（LN）的疗效，并探索潜在的分子机制。
用miR-20a慢病毒载体转染小鼠ADSCs以获得过表达miR-20a的ADSCs（miR-20a-ADSCs）。我们首先观察miR-20a对ADSC活力和凋亡的影响。30至33周龄的B6.MRL/lpr小鼠每周静脉注射ADSC/miR-20a-ADSC，狼疮组和正常对照组按相同方案注射PBS。
miR-20a在miR-20a-ADSC来源的外泌体中表达增加，miR-20a过表达促进ADSC增殖并抑制凋亡。与ADSCs相比，miR-20a-ADSC治疗显著改善了血清学和组织学异常，血清肌酐、抗双链DNA抗体、24小时尿蛋白水平、肾炎评分以及C3/IgG沉积降低证明了这一点。此外，与ADSC治疗相比，miR-20a-ADSC治疗导致Akt、mTOR和p62表达下调，miR-20a、Beclin 1和LC3 II/I表达上调。与ADSC组相比，用miR-20a-ADSC治疗后，足细胞内自噬体数量显著增加，同时足突蛋白和nephrin表达上调。
miR-20a-ADSC移植可预防狼疮性肾炎的发展并显著改善已有的疾病，其机制与通过靶向miR-20a调控的mTOR途径的自噬有关。
