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.
Marin
Ethan P
EP
Department of Nephrology, Yale University School of Medicine, New Haven, CT 06536, USA.
Moeckel
Gilbert
G
Al-Lamki
Rafia
R
Bradley
John
J
Yan
Qingshang
Q
Wang
Tong
T
Wright
Paulette L
PL
Yu
Jun
J
Sessa
William C
WC
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