The impact of autophagy on the development of senescence in primary tubular epithelial cells. Issue 21 (1st November 2016)

• Record Type: Journal Article
• Authors: Baisantry, Arpita; Bhayana, Sagar; Wrede, Christoph; Hegermann, Jan; Haller, Hermann; Melk, Anette; Schmitt, Roland
• Is Part Of: Cell cycle. Volume 15:Issue 21(2016)
• Page Start: 2973
• Page End: 2979
• Publication Date: 2016-11-01
• Subjects: Autophagy -- chloroquine -- p16INK4a -- rapamycin -- senescence -- tubular epithelial cells; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1234547
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Autophagy and senescence are 2 distinct pathways that are importantly involved in acute kidney injury and renal repair. Recent data indicate that the 2 processes might be interrelated. To investigate the potential link between autophagy and senescence in the kidney we isolated primary tubular epithelial cells (PTEC) from wild-type mice and monitored the occurrence of cellular senescence during autophagy activation and inhibition. We found that the process of cell isolation and transfer into culture was associated with a strong basal autophagic activation in PTEC. Specific inhibition of autophagy by silencing autophagy-related 5 (Atg5) counteracted the occurrence of senescence hallmarks under baseline conditions. Reduced senescent features were also observed in Atg5 silenced PTEC after γ-irradiation and during H-Ras induced oncogenic senescence, but the response was less uniform in these stress models. Senescence inhibition was paralleled by better preservation of a mature epithelial phenotype in PTEC. Interestingly, treatment with rapamycin, which acts as an activator of autophagy, also counteracted the occurrence of senescence features in PTEC. While we interpret the anti-senescent effect of rapamycin as an autophagy-independent effect of mTOR-inhibition, the more specific approach of Atg5 silencing indicates that overactivated autophagy can have pro-senescent effects in PTEC. These results highlight the complex interaction between cell culture dependent stress mechanisms, autophagy and senescence.