Department of Physiology, Shihezi University Medical College, Shihezi 832002, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi 832002, China; The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Shihezi 832002, China.
Department of Physiology, Shihezi University Medical College, Shihezi 832002, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi 832002, China; The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Shihezi 832002, China; Department of Burns department, First Affiliated Hospital of Shihezi University, Shihezi 832002, China.
Life Sci. 2021 Jun 1;274:119347. doi: 10.1016/j.lfs.2021.119347. Epub 2021 Mar 11.
Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a β-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear. Our research aims to prove the effect of Gal-3 on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMC) induced by transforming growth factor β1 (TGF-β1) and to study its mechanism. In vivo experiment: In Sprague-Dawley (SD) rats, monocrotaline was injected intraperitoneally to establish a PH model, and the Gal-3 inhibitor (modified citrus pectin, MCP) 28 Ds was administered in the stomach. The results indicate that Gal-3 and TGF-β1 may be involved in the occurrence and development of PH, which may be related to the Smad2/3 signalling pathway. In vitro experiment: Human pulmonary artery smooth muscle cells were pretreated with the Gal-3 inhibitor (MCP) for 24 h, then TGF-β1 or Gal-3 was administered to the cells for 24 h. The results show that exogenous TGF-β1 and Gal-3 can activate the downstream Smad2/3 signalling pathway, and increase the proliferation and migration ability of HPASMC. However, the Gal-3 inhibitor (MCP) inhibited these effects. Further results display that TGF-β1 and Gal-3 could mutually regulate the protein and mRNA expression levels. In summary, the results of this study indicate that Gal-3 regulates the Smad2/3 signalling pathway through protein interaction with TGF-β1, in turn regulates the proliferation and migration of HPASMC, thereby regulating the occurrence and development of PH.
肺血管重构是肺动脉高压（PH）的最重要因素之一。半乳糖凝集素-3（Gal-3）是一种β-半乳糖苷结合凝集素。在最新的文献中，Gal-3 被报道参与肺血管重构，但其潜在机制尚不清楚。我们的研究旨在证明 Gal-3 对转化生长因子β1（TGF-β1）诱导的人肺动脉平滑肌细胞（HPASMC）增殖和迁移的影响，并研究其机制。体内实验：在 Sprague-Dawley（SD）大鼠中，腹腔内注射单克隆旋毛虫建立 PH 模型，并给予胃内 Gal-3 抑制剂（改性柑橘果胶，MCP）28 Ds。结果表明，Gal-3 和 TGF-β1 可能参与 PH 的发生发展，可能与 Smad2/3 信号通路有关。体外实验：人肺动脉平滑肌细胞用 Gal-3 抑制剂（MCP）预处理 24 h，然后给予 TGF-β1 或 Gal-3 处理细胞 24 h。结果表明，外源性 TGF-β1 和 Gal-3 可激活下游 Smad2/3 信号通路，增加 HPASMC 的增殖和迁移能力。然而，Gal-3 抑制剂（MCP）抑制了这些作用。进一步的结果显示，TGF-β1 和 Gal-3 可以相互调节蛋白和 mRNA 表达水平。综上所述，本研究结果表明，Gal-3 通过与 TGF-β1 的蛋白相互作用调节 Smad2/3 信号通路，进而调节 HPASMC 的增殖和迁移，从而调节 PH 的发生发展。
