title: Activation of peroxisome proliferator-activated receptor γ inhibits vascular calcification by upregulating Klotho.
abstract: Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, which was originally identified as an aging suppressor gene, has been shown to be associated with vascular calcification. Since Klotho was recently identified as a target for nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ, the present study aimed to determine whether PPARγ regulates VSMC calcification through modulating the expression levels of Klotho. It was demonstrated that the expression of PPARγ was downregulated during Pi-induced VSMC calcification. In addition, treatment with PPARγ agonists inhibited the calcification and enhanced the expression of Klotho in VSMCs in a PPARγ-dependent manner. Of note, loss of Klotho expression by RNA interference abolished the ability of PPARγ activation to inhibit VSMC calcification. Furthermore, activation of Klotho as well as PPARγ inhibited the expression of Pi transporter 1/2 and reduced Pi influx into VSMCs. To the best of our knowledge, the present study was the first to demonstrate that PPARγ regulates VSMC calcification through activating Klotho.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Hao
keywords: Klotho; inorganic phosphate transporter 1/2; peroxisome proliferator-activated receptor γ; vascular smooth muscle cell calcification