Yan Shen, Huaxing Huang, Lianglan Shen, Wubin Yao, Rong Wang, Meizi Kang, Jiashan Huang, Yan Xie, Hongli Yang
{"title":"在慢性肾脏病中，ZBTB16通过Wnt/β-catenin通路加速血管内皮细胞成骨细胞转化，从而推动血管钙化。","authors":"Yan Shen, Huaxing Huang, Lianglan Shen, Wubin Yao, Rong Wang, Meizi Kang, Jiashan Huang, Yan Xie, Hongli Yang","doi":"10.1097/SHK.0000000000002488","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>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 cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have 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 staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR 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 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 downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"312-319"},"PeriodicalIF":2.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ZBTB16 DRIVES VASCULAR CALCIFICATION THROUGH ACCELERATING VSMCS OSTEOBLASTIC TRANSITION IN CHRONIC KIDNEY DISEASE VIA WNT/Β-CATENIN PATHWAY.\",\"authors\":\"Yan Shen, Huaxing Huang, Lianglan Shen, Wubin Yao, Rong Wang, Meizi Kang, Jiashan Huang, Yan Xie, Hongli Yang\",\"doi\":\"10.1097/SHK.0000000000002488\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Abstract: </strong>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 cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have 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 staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR 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 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 downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.</p>\",\"PeriodicalId\":21667,\"journal\":{\"name\":\"SHOCK\",\"volume\":\" \",\"pages\":\"312-319\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SHOCK\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/SHK.0000000000002488\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002488","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
ZBTB16 DRIVES VASCULAR CALCIFICATION THROUGH ACCELERATING VSMCS OSTEOBLASTIC TRANSITION IN CHRONIC KIDNEY DISEASE VIA WNT/Β-CATENIN PATHWAY.
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 cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have 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 staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR 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 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 downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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