Identification and regulation of reticulon 4B (Nogo-B) in renal tubular epithelial cells.
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.
Department of Nephrology, Yale University School of Medicine, New Haven, CT 06536, USA.
Ethan P
EP
Marin
Gilbert
G
Moeckel
Rafia
R
Al-Lamki
John
J
Bradley
Qingshang
Q
Yan
Tong
T
Wang
Paulette L
PL
Wright
Jun
J
Yu
William C
WC
Sessa
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007673:Kidney Cortex Necrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000235:genetics* / Q000378:metabolism; D000070798:Nogo Proteins; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism / Q000473:pathology
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse