title: Diabetic nephropathy and proximal tubular damage.
abstract: Diabetic nephropathy (DN) is a major cause of uremia in developed societies. Inflammation is emerging as an important mechanism for its pathogenesis and progression. Herein, we review 4 recently described cellular receptors that have been shown to mediate diabetic interstitial kidney disease. Peroxisome proliferator-activated receptor-γ attenuates STAT-1 activation and has shown promise in renoprotection. Its clinical utility is limited mainly by fluid retention through upregulation of sodium-hydrogen exchanger-3 and aquaporin-1 channels in the proximal tubule. The bradykinin receptor 2 of the kallikrein-kinin system has been shown to mediate diabetic kidney injury and its blockade conferred renoprotective effects in animal models of DN. The related protease-activated receptor, especially receptor 4, has recently been shown to participate in DN. Further studies are required to confirm its role. Finally, the toll-like receptor, especially TLR4 and TLR2, has been verified in multiple models to be a significant sensor of and reactor to hyperglycemia and other diabetic substrates that orchestrate interstitial inflammation in DN.
authors.affiliation: Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong. Electronic address: scwtang@hku.hk.
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Wai Han
authors.initials: WH
authors.lastname: Yiu
authors.affiliation: Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000503:physiopathology; D016234:Kallikrein-Kinin System / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D051381:Rats; D044462:Receptors, Proteinase-Activated / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D044462:Receptors, Proteinase-Activated; D051193:Toll-Like Receptors