TGF-β1/Smad3 signaling promotes collagen synthesis in pulmonary artery smooth muscle by down-regulating miR-29b

被引:5
作者
Wang, Tingxia [1 ]
Li, Yun [1 ]
Chen, Juan [1 ]
Xie, Lijian [1 ]
Xiao, Tingting [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Childrens Hosp, Dept Cardiol, 355 Lu Ding Rd, Shanghai 200062, Peoples R China
关键词
miR-29b; collagen synthesis; TGF-beta; 1; Smad3; PASMCs; HYPERTENSION; FIBROSIS; FAMILY; MYOFIBROBLASTS; MICRORNA-29; MECHANISMS; EXPRESSION; APOPTOSIS; MATRIX;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Deposition of fibronectin and collagen in the extracellular matrix (ECM) and the proliferation, migration, and hypertrophy of vascular smooth muscle cells (VSMCs) result in pulmonary arterial (PA) hypertrophy and muscularization, leading to increased pulmonary vascular resistance in pulmonary arterial hypertension (PAH). MicroR-NA29 (miR-29) is reported to be associated with diseases such as liver fibrosis, renal fibrosis, pulmonary fibrosis, and cardiac fibrosis in which collagen synthesis plays an important role. Due to the possible link between PAH and collagen, in this study, we examined the role and therapeutic potential of miR-29b in vitro and in a rat model of pulmonary hypertension induced by monocrotaline (MCT). Results revealed that miR-29b treatment PAH rats showed a lower level of collagen synthesis. Furthermore, in pulmonary arterial smooth muscle cells (PASMCs), TGF beta 1/Smad3 signaling negatively regulated the expression of miR-29b, and miR-29b suppressed collagen synthesis by directly targeting collagen I and blocking PI3K/AKT signaling. In addition, TGF-beta 1/Smad3 signaling promoted collagen synthesis in PASMCs by down-regulating miR-29b. Interestingly, Smad3 decreased the expression of miR-29b by interacting with its promotor. In conclusion, our results revealed that miR-29b plays an important role in collagen synthesis and may be a therapeutic target for PAH when regulated by the TGF-beta 1/Smad3 pathway.
引用
收藏
页码:5592 / +
页数:12
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