4.5 Article

MicroRNA-155 Suppresses Mesangial Cell Proliferation and TGF-1 Production via Inhibiting CXCR5-ERK Signaling Pathway in Lupus Nephritis

Journal

INFLAMMATION
Volume 42, Issue 1, Pages 255-263

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-018-0889-1

Keywords

CXCL13; miR-155; mesangial cell; lupus nephritis

Funding

  1. National Natural Science Foundation of China [81601410]
  2. Jiangsu Provincial Commission of Health and Family Planning [H201623]
  3. Special Fund for Clinical Medical Science and Technology of Nantong [HS2014071, HS2016003]

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Increasing evidence shows miR-155 plays an important role in regulating inflammatory processes in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). Because the chemokine CXCL13 is implicated in the pathogenesis of LN, here we examined whether miR-155 can modulate the activity of CXCL13 or its receptor CXCR5. We determined the expression of CXCL13 in normal and MRL/lpr mice and found elevated levels of CXCL13 in the kidneys of MRL/lpr mice compared with normal kidneys. Besides, CXCL13 expression was mainly detected in the glomerulus, specifically to mesangial areas. We then transfected a miR-155 mimic in human renal mesangial cells (HRMCs) to overexpress miR-155 and detected decreased protein levels of CXCR5 by western blot analysis. Transfection of the miR-155 mimic into CXCL13-treated HRMCs resulted in a significantly reduced proliferation rate of HRMCs as measured by the cell-counting assay and flow cytometry. Moreover, increased intracellular miR-155 also led to decreased phosphorylation of ERK and TGF-1 production. Together, these results revealed that miR-155 may play a role in the pathogenesis of LN.

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