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The pathological significance of dipeptidyl peptidase-4 in endothelial cell homeostasis and kidney fibrosis

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Abstract

Endothelial dysfunction and tubulointerstitial fibrosis are characteristics of diabetic kidneys. Recent evidence has suggested that the diabetic kidney is associated with dipeptidyl peptidase (DPP)-4 overexpression in endothelial cells. Several insults can induce endothelial cells to alter their phenotype into a mesenchymal-like phenotype via endothelial–mesenchymal transition (EndMT), which plays pivotal roles in tissue fibrosis. We have recently revealed the fibrogenic role of DPP-4 through the induction of EndMT in diabetic kidneys. This review mainly focuses on the biological and pathological significance of DPP-4 overexpression in endothelial cells through the mechanisms of endothelial homeostasis defects, EndMT, and kidney fibrosis.

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Acknowledgments

Parts of this review were presented in the Lilly Award Lecture at the Japan Diabetes Society 2016, Kyoto, Japan. KK would like to express his sincere gratitude to Professor Daisuke Koya for his guidance and support. This work was partially supported by grants from the Japan Society for the Promotion of Science to KK (23790381) and research grants from the Japan Research Foundation for Clinical Pharmacology to KK (2011). This work was partially supported by a Grant for Promoted Research awarded to KK (S2013-13, S2014-4, S2015-3) from Kanazawa Medical University.

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  1. Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Keizo Kanasaki

  2. Division of Anticipatory Molecular Food Science and Technology, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Keizo Kanasaki

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Correspondence to Keizo Kanasaki.

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KK received lecture fees from Boehringer Ingelheim and Eli Lilly. Both Boehringer Ingelheim and Eli Lilly donated funds to Kanazawa Medical University and were not directly associated with this project. Boehringer Ingelheim, Mitsubishi Tanabe Pharma, and Ono Pharmaceutical contributed funds to establish the Division of Anticipatory Molecular Food Science and Technology. KK is in a consulting contract with Boehringer Ingelheim.

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Kanasaki, K. The pathological significance of dipeptidyl peptidase-4 in endothelial cell homeostasis and kidney fibrosis. Diabetol Int 7, 212–220 (2016). https://doi.org/10.1007/s13340-016-0281-z

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