MicroRNA-16 directly binds to DEC2 and inactivates the TLR4 signaling pathway to inhibit lupus nephritis-induced kidney tissue hyperplasia and mesangial cell proliferation
MicroRNA-16 directly binds to DEC2 and inactivates the TLR4 signaling pathway to inhibit lupus nephritis-induced kidney tissue hyperplasia and mesangial cell proliferation
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MicroRNA-16直接结合DEC2并失活TLR4信号通路抑制狼疮肾炎诱导的肾组织增生和系膜细胞增殖
DOI：
10.1016/j.intimp.2020.106859
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发表时间：
2020-11-01
影响因子：
5.6
通讯作者：
Liu, Qiang
中科院分区：
文献类型：
--
作者：
Qi, Huimeng;Cao, Qin;Liu, Qiang
狼疮性肾炎(LN)是系统性红斑狼疮(SLE)最严重的表现，也是死亡的主要风险。本研究旨在探讨microRNA-16(miR-16)在LN发育中的作用。使用FcGamma受体II-b缺陷(Fcgr2b(-/-))小鼠，这些小鼠具有发生SLE和LN样疾病的自然潜力。通过功能获得和功能丧失的研究，探讨miR-16在小鼠肾组织病理症状和系膜细胞(SV40MES-13)增殖中的作用。探索了miR-16可能的下游分子。因此，miR-16在肾脏组织中的表达很低。上调miR-16可抑制小鼠肾组织的组织增生、炎性浸润、肾小球损伤和纤维化，增加细胞凋亡，抑制MES-13细胞的增殖，促进细胞的凋亡。MIR-16直接与DEC2结合，使TLR4信号失活。DEC2阻断miR-16对MES-13细胞的保护作用。抑制miR-16对MES-13细胞增殖的促进作用可被TLR4拮抗剂氯喹逆转。综上所述，miR-16通过抑制DEC2沉默和TLR4信号转导缺陷，减轻肾组织LN症状，减少系膜细胞增殖，从而对LN有较强的保护作用。
Lupus nephritis (LN) is the most serious manifestation of systemic lupus erythematosus (SLE) and a major risk of mortality. This research focused on the function of microRNA-16 (miR-16) in LN development. Fcgamma receptor II-b-deficient (Fcgr2b(-/-)) mice with the natural potential to develop SLE- and LN-like diseases were used. Gain- and loss-of-function studies were performed to explore the function of miR-16 in pathological symptoms in mouse kidney tissues and the proliferation of mesangial cells (SV40 MES-13). The putative downstream molecules of miR-16 were explored. Consequently, poor expression of miR-16 was found in kidney tissues. Upregulation of miR-16 inhibited tissue hyperplasia, inflammatory infiltration, glomerular injury and fibrosis but increased cell apoptosis in mouse kidney tissues, and it inhibited proliferation but promoted apoptosis of MES-13 cells as well. miR-16 directly bound to DEC2 and inactivated the TLR4 signaling. DEC2 blocked the protective roles of miR-16 in MES-13 cells. The enhanced proliferation in MES-13 cells following miR-16 inhibition was reversed by chloroquine phosphate, a TLR4 antagonist. To sum up, miR-16 was evidenced to have a potent protective capacity in LN through relieving the LN symptoms in kidney tissues and reducing proliferation of mesangial cells, during which DEC2 silencing and TLR4 signaling deficit were involved.