Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.
10.26599/1671-5411.2023.06.002
- Author:
Jing YU
1
;
Wen-Zhao YAN
2
;
Xin-Hua ZHANG
1
;
Bin ZHENG
1
;
Wen-Sen PAN
3
;
Zhan YANG
1
;
Hong ZHANG
4
;
Zi-Yuan NIE
5
;
Ying MA
6
;
Yang BAI
1
;
Long ZHANG
1
;
Dan-Dan FENG
1
;
Jin-Kun WEN
1
Author Information
1. Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China.
2. Department of Infectious Diseases, the Third Hospital of Hebei Medical University, Shijiazhuang, China.
3. Second Department of Respiratory and Critical Care Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
4. Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
5. Department of Hematology, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
6. Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, China.
- Publication Type:Journal Article
- From:
Journal of Geriatric Cardiology
2023;20(6):431-447
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying 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 I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. 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 downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced 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 that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis 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.
