Galectin-3: A Harbinger of Reactive Oxygen Species, Fibrosis, and Inflammation in Pulmonary Arterial Hypertension
Galectin-3: A Harbinger of Reactive Oxygen Species, Fibrosis, and Inflammation in Pulmonary Arterial Hypertension
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DOI：
10.1089/ars.2019.7753
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发表时间：
2019-03-29
影响因子：
6.6
通讯作者：
Barman, Scott A.
中科院分区：
文献类型：
--
作者：
Fulton, David J. R.;Li, Xueyi;Barman, Scott A.
关键问题：目前还没有治愈PAH的方法，也没有有效阻止或逆转PA重塑的干预措施，过去几十年的深入研究试图确定具有治疗价值的新分子机制。最新进展：半乳糖凝集素-3（Galectin-3，Gal-3）是一种糖结合凝集素，其显著的嵌合结构由N-末端寡聚化结构域和C-末端糖识别结构域组成。Gal-3已被确定为导致异常PA重塑（包括细胞增殖、炎症和纤维化）的许多细胞行为变化的调节剂，但其在PAH中的作用直到最近仍知之甚少。相比之下，已经提出了Gal-3在癌症和炎性和纤维增生性疾病（例如肺血管和心脏纤维化）中的病理作用。本文就Gal-3在PAH发生发展中的作用进行综述。我们提供的实验证据支持Gal-3影响活性氧产生、NADPH氧化酶表达和氧化还原信号传导的能力，这已被证明有助于血管重塑和肺动脉压升高。未来发展方向：虽然几项临床前研究表明Gal-3促进高血压肺血管重塑，但Gal-3在人类PAH中的临床意义仍有待确定。抗氧化剂。氧化还原信号。00，000-000。
Critical Issues: There is no cure for PAH nor interventions that effectively arrest or reverse PA remodeling, and intensive research over the past several decades has sought to identify novel molecular mechanisms of therapeutic value. Recent Advances: Galectin-3 (Gal-3) is a carbohydrate-binding lectin remarkable for its chimeric structure, composed of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 has been identified as a regulator of numerous changes in cell behavior that contributes to aberrant PA remodeling, including cell proliferation, inflammation, and fibrosis, but its role in PAH has remained poorly understood until recently. In contrast, pathological roles for Gal-3 have been proposed in cancer and inflammatory and fibroproliferative disorders, such as pulmonary vascular and cardiac fibrosis. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH. We provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species production, NADPH oxidase enzyme expression, and redox signaling, which have been shown to contribute to both vascular remodeling and increased pulmonary arterial pressure. Future Directions: While several preclinical studies suggest that Gal-3 promotes hypertensive pulmonary vascular remodeling, the clinical significance of Gal-3 in human PAH remains to be established. Antioxid. Redox Signal. 00, 000-000.