The activity and role of autophagy in the pathogenesis of diabetic nephropathy

W.-J. Liu, W.-F. Huang, L. Ye, R.-H. Chen, C. Yang, H.-L. Wu, Q.-J. Pan, H.-F. Liu

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China. hf-liu@263.net

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• Metabolism

OBJECTIVE: Evidence suggested that deficiency of autophagy is involved in the pathogenesis of diabetic nephropathy (DN). However, some recent studies have also shown that autophagy is activated in renal cells under diabetic conditions. In this review, we discuss whether autophagy is inactivated in renal cells in DN as well as the therapeutic potential of autophagy for treating DN, in order to aid future investigation in this field.

MATERIALS AND METHODS: Relevant information, original research articles and reviews, were gathered primarily through a search in PubMed and Cochrane database. The activity and role of autophagy, as well as the relevant signaling pathways, were analyzed in different intrinsic renal cells, including podocyte, renal tubular epithelial cell, glomerular mesangial and endothelial cells.

RESULTS: The upstream of autophagic pathway, but not whole pathway, was predominately studied in these intrinsic renal cells, such as the induction of autophagy, an amount of autophagic vacuoles and so on. In most cases, autophagic inactivation occurred, which is an important mechanism underlying DN progression. Targeting the autophagic pathway to activate autophagy activity might have renoprotective effect. However, autophagic activation was also found in a few studies, in which there was a debate on the role of activated autophagy: mounting an adaptive response or leading to autophagic apoptosis.

CONCLUSIONS: The downstream of autophagic pathway, including the degradation of autophagic vacuoles, and lysosomal function, should be well studied to clarify the activity and role of autophagy in the progression of DN. Autophagy activation is likely a potential therapy for combatting DN.

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