RESUMEN
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.
Asunto(s)
Células Epiteliales/metabolismo , Túbulos Renales/metabolismo , Proteínas de la Mielina/genética , Animales , Movimiento Celular/genética , Células Epiteliales/patología , Células Epiteliales/fisiología , Regulación de la Expresión Génica/fisiología , Humanos , Necrosis de la Corteza Renal/genética , Necrosis de la Corteza Renal/metabolismo , Necrosis de la Corteza Renal/patología , Médula Renal/metabolismo , Médula Renal/patología , Necrosis Papilar Renal/genética , Necrosis Papilar Renal/metabolismo , Necrosis Papilar Renal/patología , Túbulos Renales/patología , Túbulos Renales/fisiología , Macrófagos/metabolismo , Macrófagos/patología , Macrófagos/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de la Mielina/metabolismo , Proteínas Nogo , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patologíaRESUMEN
Sixteen members of three families, eight of which had vesicoureteral reflux, are studied. Authors report a high incidence in females (7 cases) and atrophic chronic pyelonephritis (75% of the serie). Only one girl presented disminution of renal function. The types of inheritance was dominant autosomal in the A family and autosomal recessive in the B and C families. Finally the norms of investigation of the familial vesicoureteral reflux are appointed.
