CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish

Abstract Background CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the p...

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Veröffentlicht in:International journal of cardiology 2016-07, Vol.214, p.246-253
Hauptverfasser: Peng, Xiyang, Li, Guanming, Wang, Yuequn, Zhuang, Jian, Luo, Rong, Chen, Jimei, Chen, Fa, Shi, Yan, Li, Jiani, Zhou, Zuoqiong, Mo, Xiaoyang, Liu, Xianchu, Yuan, Wuzhou, Zeng, Qun, Li, Yongqing, Jiang, Zhigang, Wan, Yongqi, Ye, Xiangli, Xu, Wei, Wang, Xijun, Fan, Xiongwei, Zhu, Ping, Wu, Xiushan, Deng, Yun
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container_issue
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container_title International journal of cardiology
container_volume 214
creator Peng, Xiyang
Li, Guanming
Wang, Yuequn
Zhuang, Jian
Luo, Rong
Chen, Jimei
Chen, Fa
Shi, Yan
Li, Jiani
Zhou, Zuoqiong
Mo, Xiaoyang
Liu, Xianchu
Yuan, Wuzhou
Zeng, Qun
Li, Yongqing
Jiang, Zhigang
Wan, Yongqi
Ye, Xiangli
Xu, Wei
Wang, Xijun
Fan, Xiongwei
Zhu, Ping
Wu, Xiushan
Deng, Yun
description Abstract Background CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. Methods and results Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5 , hand2 , and has2 . Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects. Conclusion Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. This finding suggested that CXXC5 may serve as a possible marker that has potential diagnostic and prognostic value in fetus with congenital heart disease.
doi_str_mv 10.1016/j.ijcard.2016.03.201
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Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. Methods and results Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5 , hand2 , and has2 . Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects. Conclusion Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. This finding suggested that CXXC5 may serve as a possible marker that has potential diagnostic and prognostic value in fetus with congenital heart disease.</description><identifier>ISSN: 0167-5273</identifier><identifier>EISSN: 1874-1754</identifier><identifier>DOI: 10.1016/j.ijcard.2016.03.201</identifier><identifier>PMID: 27077543</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>Animals ; Binding Sites ; Cardiogenesis ; Cardiovascular ; Cell Line ; Congenital heart diseases ; CXXC5 ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - metabolism ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins - chemistry ; Intracellular Signaling Peptides and Proteins - metabolism ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Protein Binding ; Rats ; Signal Transduction ; Smad Proteins - chemistry ; Smad Proteins - metabolism ; Tgfβ signaling pathway ; Transforming Growth Factor beta - metabolism ; Zebrafish - metabolism ; Zebrafish Proteins - chemistry ; Zebrafish Proteins - metabolism</subject><ispartof>International journal of cardiology, 2016-07, Vol.214, p.246-253</ispartof><rights>2016 Elsevier Ireland Ltd</rights><rights>Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</citedby><cites>FETCH-LOGICAL-c450t-76a4d58b0f3f2ff041846f6845112781c82c1bf493c6d309fa82156f3f4c2bfe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0167527316306684$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27077543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Xiyang</creatorcontrib><creatorcontrib>Li, Guanming</creatorcontrib><creatorcontrib>Wang, Yuequn</creatorcontrib><creatorcontrib>Zhuang, Jian</creatorcontrib><creatorcontrib>Luo, Rong</creatorcontrib><creatorcontrib>Chen, Jimei</creatorcontrib><creatorcontrib>Chen, Fa</creatorcontrib><creatorcontrib>Shi, Yan</creatorcontrib><creatorcontrib>Li, Jiani</creatorcontrib><creatorcontrib>Zhou, Zuoqiong</creatorcontrib><creatorcontrib>Mo, Xiaoyang</creatorcontrib><creatorcontrib>Liu, Xianchu</creatorcontrib><creatorcontrib>Yuan, Wuzhou</creatorcontrib><creatorcontrib>Zeng, Qun</creatorcontrib><creatorcontrib>Li, Yongqing</creatorcontrib><creatorcontrib>Jiang, Zhigang</creatorcontrib><creatorcontrib>Wan, Yongqi</creatorcontrib><creatorcontrib>Ye, Xiangli</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Wang, Xijun</creatorcontrib><creatorcontrib>Fan, Xiongwei</creatorcontrib><creatorcontrib>Zhu, Ping</creatorcontrib><creatorcontrib>Wu, Xiushan</creatorcontrib><creatorcontrib>Deng, Yun</creatorcontrib><title>CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish</title><title>International journal of cardiology</title><addtitle>Int J Cardiol</addtitle><description>Abstract Background CXXC-type zinc-finger protein CXXC5 has been reported to be associated with the development of cardiovascular disease. Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. Methods and results Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5 , hand2 , and has2 . Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects. Conclusion Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. 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Recently, through signaling pathway screening we found that CXXC5 activated Tgfβ and myocardial differentiation signaling pathways simultaneously. Although the physiological and pathological function of CXXC5 in many organs has been well elucidated, its function in heart remains unclear. Methods and results Here, we found that zebrafish CXXC5 and SMAD were interacting through ZF-CXXC and MH1 domain. Over-expression of CXXC5 in cardiomyocyte increased the luciferase report activity of Tgfβ signaling pathway. Spatiotemporal expression profile of cxxc5 showed that it consistently expressed during cardiogenesis. Knockdown of cxxc5 in zebrafish displayed looping defects, cardiac dysplasia, pericardial edema, and decreased contraction ability, accompanied with down-regulation of members referring to cardiac looping downstream genes of Tgfβ signaling pathway, such as nkx2.5 , hand2 , and has2 . Co-injection of hand2 mRNA with cxxc5 morpholino rescued the cardiac looping detects. Conclusion Our study is the first to provide an in vivo evidence for cxxc5 regulating heart development and cardiac looping via Tgfβ related signaling pathway. This finding suggested that CXXC5 may serve as a possible marker that has potential diagnostic and prognostic value in fetus with congenital heart disease.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>27077543</pmid><doi>10.1016/j.ijcard.2016.03.201</doi><tpages>8</tpages></addata></record>
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subjects Animals
Binding Sites
Cardiogenesis
Cardiovascular
Cell Line
Congenital heart diseases
CXXC5
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins - chemistry
Intracellular Signaling Peptides and Proteins - metabolism
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Protein Binding
Rats
Signal Transduction
Smad Proteins - chemistry
Smad Proteins - metabolism
Tgfβ signaling pathway
Transforming Growth Factor beta - metabolism
Zebrafish - metabolism
Zebrafish Proteins - chemistry
Zebrafish Proteins - metabolism
title CXXC5 is required for cardiac looping relating to TGFβ signaling pathway in zebrafish
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