Identification and regulation of reticulon 4B (Nogo-B) in renal tubular epithelial cells

Am J Pathol. 2010 Dec;177(6):2765-73. doi: 10.2353/ajpath.2010.100199. Epub 2010 Oct 22.


Nogo-B is a member of the reticulon family of proteins that has been implicated in diverse forms of vascular injury. Although Nogo-B is expressed in renal tissues, its localization and function in the kidney have not been examined. Here, we report that Nogo-B is expressed specifically in the epithelial cells of the distal nephron segments in the murine kidney. After unilateral ureteral obstruction (UUO) and ischemia/reperfusion, Nogo-B gene and protein levels increased dramatically in the kidney. This increase was driven in part by injury-induced de novo expression in proximal tubules. Examination of Nogo-B immunostaining in human biopsy specimens from patients with acute tubular necrosis showed similar increases in Nogo-B in cortical tubules. Mice genetically deficient in Nogo-A/B were indistinguishable from wild-type (WT) mice based on histological appearance and serum analyses. After UUO, there was a significant delay in recruitment of macrophages to the kidney in the Nogo-A/B-deficient mice. However, measurements of fibrosis, inflammatory gene expression, and histological damage were not significantly different from WT mice. Thus, Nogo-B is highly expressed in murine kidneys in response to experimental injuries and may serve as a marker of diverse forms of renal injury in tissues from mice and humans. Furthermore, Nogo-B may regulate macrophage recruitment after UUO, although it does not greatly affect the degree of tissue injury or fibrosis in this model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / physiology
  • Gene Expression Regulation / physiology
  • Humans
  • Kidney Cortex Necrosis / genetics
  • Kidney Cortex Necrosis / metabolism
  • Kidney Cortex Necrosis / pathology
  • Kidney Medulla / metabolism
  • Kidney Medulla / pathology
  • Kidney Papillary Necrosis / genetics
  • Kidney Papillary Necrosis / metabolism
  • Kidney Papillary Necrosis / pathology
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Proteins / genetics*
  • Myelin Proteins / metabolism
  • Nogo Proteins
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / metabolism
  • Ureteral Obstruction / pathology


  • Myelin Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, mouse