1. Academic Validation
  2. 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

  • Int Immunopharmacol. 2020 Nov;88:106859. doi: 10.1016/j.intimp.2020.106859.
Huimeng Qi 1 Qin Cao 2 Qiang Liu 3
Affiliations

Affiliations

  • 1 Department of General Practice, the First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
  • 2 Department of Gastroenterology, the First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China.
  • 3 Department of Nephrology, the First Hospital of China Medical University, Shenyang 110001, Liaoning, PR China. Electronic address: torroseliu@163.com.
Abstract

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.

Keywords

DEC2; Hyperplasia; Lupus nephritis; MicroRNA-16; Systemic lupus erythematosus; TLR4 signaling pathway.

Figures
Products