Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type Ⅰ collagen expression
Jing YU1
Wen-Zhao YAN2
Xin-Hua ZHANG3
Bin ZHENG4
Wen-Sen PAN5
Zhan YANG6
Hong ZHANG7
Zi-Yuan NIE8
Ying MA9
Yang BAI4
Long ZHANG4
Dan-Dan FENG4
Jin-Kun WEN4
1.Department of Biochemistry and Molecular Biology,Hebei Medical University,Shijiazhuang,China;Second Depart-ment of Respiratory and Critical Care Medicine,the Second Hospital of Hebei Medical University,Shijiazhuang,China2.De-partment of Infectious Diseases,the Third Hospital of Hebei Medical University,Shijiazhuang,China3.Department of Biochemistry and Molecular Biology,Hebei Medical University,Shijiazhuang,China;Institution of Chinese Integrative Medicine,Hebei Medical University,Shijiazhuang,China4.Department of Biochemistry and Molecular Biology,Hebei Medical University,Shijiazhuang,China5.Second Depart-ment of Respiratory and Critical Care Medicine,the Second Hospital of Hebei Medical University,Shijiazhuang,China6.Department of Biochemistry and Molecular Biology,Hebei Medical University,Shijiazhuang,China;Department of Urology,the Second Hospital of Hebei Medical University,Shijiazhuang,China7.Department of Urology,the Second Hospital of Hebei Medical University,Shijiazhuang,China8.Department of Hematology,the Second Hospital of Hebei Medical University,Shijiazhuang,China9.Department of Biochemistry and Molecular Biology,Binzhou Medical University,Yantai,China
摘要：BACKGROUND Abnormal type Ⅰ collagen(COL1)expression is associated with the development of many cardiovascular dis-eases.The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression,but the underl-ying molecular mechanisms are still not fully understood.METHODS Gain-and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type 1 collagen(COL1A2).Co-immunoprecipitation assay was performed to observe the interaction between two prot-eins.RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.RESULTS In this study,we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells(VSMCs).We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by down-regulating KLF4 expression through activation of the Smad signaling pathway.CircZBTB46 inhibits the expression of COL1A2 in-duced by TGF-beta.Mechanistically,circZBTB46 mediates the interaction between Smad2 and PDLIM5,resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression.Furthermore,we found that the expression of TGF-beta and COL1A2 is decreased,while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues,indicating th-at circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular ho-meostasis and aneurysm development.CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs,highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.
机标关键词：expressioncollagenaxiscirczbtb46down-regulationinhibitsignalingsmad2-pdlim5
论文发表日期：2023-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：17( 431-447 )