A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation

Sci Rep. 2016 May 16;6:25955. doi: 10.1038/srep25955.


Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / chemically induced*
  • Albuminuria / genetics
  • Albuminuria / immunology
  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / immunology*
  • Disease Models, Animal
  • Gene Knockout Techniques
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / immunology
  • Lipopolysaccharides / adverse effects*
  • Mice
  • Podocytes / cytology
  • Podocytes / metabolism*
  • Semaphorins / genetics
  • Semaphorins / metabolism*
  • Signal Transduction
  • Streptozocin


  • Cytokines
  • Lipopolysaccharides
  • Semaphorins
  • semaphorin 3G, human
  • semaphorin 3G, mouse
  • Streptozocin