HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload

Jin Tan1*, Miaohong Wang1*, Shuling Song1, Yuyang Miao2 and Qiang Zhang1

1Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Institute of Geriatrics and 2Tianjin Medical University, Tianjin, China
*These authors contributed equally to this work

Offprint requests to: Qiang Zhang, Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Institute of Geriatrics, No.154 Anshan Road, Heping District, Tianjin 300052, China. e-mail: zhangqiangyulv@163.com


Summary. Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload. Histol Histopathol 33, 681-690 (2018)

Key words: Urinary albumin, Tubular epithelial cells, Autophagy, Mitochondrial damage, Apoptosis

DOI: 10.14670/HH-11-962