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Autophagy in Proximal Tubules Prevents Or Promotes Tubular Damage Depending on The Type of Acute Kidney Injury Model
Author(s) -
Bhayana Sagar,
Baisantry Arpita,
Rong Song,
Haller Hermann,
Melk Annette,
Schmitt Roland
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.807.6
Subject(s) - atg5 , autophagy , kidney , immunostaining , inflammation , acute kidney injury , fibrosis , medicine , kidney disease , renal function , context (archaeology) , endocrinology , pathology , apoptosis , chemistry , biology , immunohistochemistry , biochemistry , paleontology
While several studies have reported protective short‐term effects of tubular autophagy during acute kidney injury (AKI), recent evidence suggests that autophagy might become detrimental leading to destructive long‐term outcome if activated in severely damaged cells.The possibility of a dual role of autophagy led us to the goal of this study to test the long‐term impact of tubular autophagic activation in the context of different models of AKI. Mice with tamoxifen inducible Atg5 gene deletion in the proximal tubular S3 segment were subjected to AKI by ischemia/reperfusion (I/R) or injection of aristolochic acid (AA).In Atg5 ‐/‐ kidneys immunostaining and electron microscopy revealed functional ablation of autophagy specifically in tubular cells of proximal S3 segment. While acute tubular damage was mostly restricted to the S3 segment in the I/R model, AA induced injury was found throughout the kidney. In the I/R model Atg5 ‐/‐ kidneys showed better recovery of renal function and significantly less chronic damage and a marked reduction in inflammation, fibrosis and cellular senescence at day 30. But, in the AA model Atg5 ‐/‐ kidneys showed only small differences to wildtypes with a tendency for stronger loss of renal function and higher chronic renal damage load at day 30.Restricted ablation of autophagy prevents chronic damage in the case of renal I/R while little effect in the AA model. These findings states that the outcome of autophagic activation strongly depends on the type of stress, the localization and the severity of damage. A deeper understanding of the mechanism is required ior developing potential strategies in AKI treatment.