Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury
| Autor: | Michael G. Janech, Evelyn Bruner, Deepak Nihalani, Megan P. Hicks, Milos N. Budisavljevic, Ehtesham Arif, Jessalyn Rodgers, Juan Carlos Q. Velez, Wayne R. Fitzgibbon, John M. Arthur, Carl Atkinson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty education Kidney Glomerulus Nephron urologic and male genital diseases Glutamyl Aminopeptidase Podocyte Nephrin 03 medical and health sciences Mice Internal medicine mental disorders medicine Animals Mice Knockout Kidney biology business.industry urogenital system Glomerulosclerosis General Medicine medicine.disease Angiotensin II Rats 030104 developmental biology medicine.anatomical_structure Endocrinology Basic Research Nephrology biology.protein Tubulointerstitial fibrosis Albuminuria Kidney Diseases Disease Susceptibility medicine.symptom business psychological phenomena and processes |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 28(7) |
| ISSN: | 1533-3450 |
| Popis: | Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases. |
| Databáze: | OpenAIRE |
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