Abstract
Chronic kidney disease (CKD)-related vascular calcification (VC) is a common degenerative phenomenon of the vessel wall and its pathological basis is the phenotypic transformation of vascular smooth muscle cell (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack) and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) has been reported to be expressed in the aortic tissues in a rat model of VC. This work is conducted to reveal the functions of ZBTB16 on VC in CKD and to probe its involved reaction mechanisms. In vivo CKD rat models were established by adenine and VSMC calcification were stimulated with high phosphate (Pi) in vitro. Renal function indexes were estimated with relevant assay kits. Renal tissues were histologically examined with Hematoxylin and Eosin (H&E) staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR (RT-qPCR) and western blot were used to detect ZBTB16 expression. Western blot, immunohistochemistry and immunofluorescence staining were used to detect osteogenic markers and smooth muscle cell markers. Western blot was used to measure the expressions of proteins implicated in Wnt/β-catenin pathway. In the blood samples of CKD patients with VC, aortic tissues of CKD rats and Pi-treated VSMCs, ZBTB16 expression was significantly increased. ZBTB16 knockdown reduced renal dysfunction, calcium deposition and inhibited VSMCs osteoblast differentiation in both in vitro and in vivo. Moreover, silencing with ZBTB16 inactivated Wingless-related integration site (Wnt)/β-catenin pathway. LiCl (Wnt/β-catenin agonist) reversed the protective effects of ZBTB16 knockdown on the calcification and osteoblastic transformation in vitro. Together, ZBTB16 silencing may down-regulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.
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