MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis

Kidney Blood Press Res. 2019;44(4):643-655. doi: 10.1159/000500923. Epub 2019 Aug 20.

Abstract

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism.

Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN).

Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased.

Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

Keywords: Human vascular smooth muscle cells; Lupus nephritis; MicroRNA-145; PDGF-BB; Renal vascular lesion; Systemic lupus erythematosus.

MeSH terms

  • Adolescent
  • Apoptosis / drug effects
  • Becaplermin / pharmacology
  • Blood Vessels / cytology
  • Blood Vessels / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Kidney / blood supply
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / etiology
  • Lupus Nephritis / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Transfection

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • Becaplermin