Semaphorin-3C Is Upregulated in Polycystic Kidney Epithelial Cells and Inhibits Angiogenesis of Glomerular Endothelial Cells

Am J Nephrol. 2020;51(7):556-564. doi: 10.1159/000508263. Epub 2020 Jul 1.

Abstract

Background: Polycystic kidney disease (PKD) is a hereditary disease characterized by cyst formation in the kidneys bilaterally. It has been observed that semaphorin-3C (SEMA3C) is overexpressed in polycystic kidney epithelial cells. It is hypothesized that upregulated SEMA3C would contribute to survival of polycystic kidney epithelial cells. Furthermore, as the kidney is a highly vascularized organ, the secreted SEMA3C from PKD epithelial cells will affect glomerular endothelial cells (GECs) in a paracrine manner.

Methods: To evaluate the effect of SEMA3C on renal cells, siSEMA3C-treated PKD epithelial cells were used for further analysis, and GECs were exposed to recombinant SEMA3C (rSEMA3C). Also, co-culture and treatment of conditioned media were employed to confirm whether PKD epithelial cells could influence on GECs via SEMA3C secretion.

Results: SEMA3C knockdown reduced proliferation of PKD epithelial cells. In case of GECs, exposure to rSEMA3C decreased angiogenesis, which resulted from suppressed migratory ability not cell proliferation.

Conclusions: This study indicates that SEMA3C is the aggravating factor in PKD. Thus, it is proposed that targeting SEMA3C can be effective to mitigate PKD.

Keywords: Angiogenesis; Polycystic kidney disease; Proliferation; Semaphorin-3c.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media / metabolism
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Gene Knockdown Techniques
  • Humans
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / pathology*
  • Neovascularization, Physiologic*
  • Polycystic Kidney Diseases / drug therapy
  • Polycystic Kidney Diseases / pathology*
  • Recombinant Proteins / metabolism
  • Semaphorins / antagonists & inhibitors
  • Semaphorins / genetics
  • Semaphorins / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • Culture Media
  • Recombinant Proteins
  • Sema3C protein, human
  • Semaphorins