Chakrabarti Mrinmay, Phillips Mollie, Dhar Rana, Herron Ansley, Kubinak Jason L, Wilson Kiesha, Murphy E Angela, Azhar Mohamad, Evans Colin E
Cardiovascular Translational Research Center, University of South Carolina School of Medicine, Columbia, South Carolina, United States.
Department of Chemical Engineering, College of Engineering and Computing, University of South Carolina, Columbia, South Carolina, United States.
Am J Physiol Lung Cell Mol Physiol. 2025 Nov 1;329(5):L539-L554. doi: 10.1152/ajplung.00154.2025. Epub 2025 Sep 8.
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are inflammatory conditions with substantial rates of morbidity and mortality, but no effective treatments. The lack of effective treatments and unacceptably high mortality rates for ARDS are partly due to an incomplete understanding of the mechanisms that control ALI/ARDS and subsequent vascular repair. Transforming growth factors (TGFs) are a class of growth factors that regulate the vascular response to inflammation, including migration, proliferation, and differentiation of cells comprising the lung vasculature. Here we review studies that describe the impact of the TGF family on inflammatory lung injury and subsequent vascular repair and fibrosis. We highlight gaps in understanding TGF isoform-specific roles in ALI/ARDS and outline directions for future research in the field of TGF-dependent regulation of inflammatory lung injury and vascular repair. Functional roles of the TGFs have been investigated in ALI/ARDS pathogenesis and pulmonary fibrosis, with a predominance for studies showing a proinjurious and profibrotic impact of TGF-β1. Studies have also shown that TGF-α is positively associated with inflammatory lung injury and fibrosis. However, the contributions of TGF-β2 and TGF-β3 to ALI/ARDS are unclear, and the contributions of all the TGF isoforms to vascular repair after ALI/ARDS are not well characterized. Improved understanding of the regulation of inflammatory lung injury and repair by the TGFs could lead to the development of a safe and effective treatment strategy for patients with ALI/ARDS.
急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）是具有较高发病率和死亡率的炎症性疾病，但尚无有效的治疗方法。ARDS缺乏有效治疗方法且死亡率高得令人难以接受，部分原因是对控制ALI/ARDS及后续血管修复的机制了解不全面。转化生长因子（TGFs）是一类调节血管对炎症反应的生长因子，包括肺血管组成细胞的迁移、增殖和分化。在此，我们综述了描述TGF家族对炎症性肺损伤及后续血管修复和纤维化影响的研究。我们强调了在理解TGF异构体在ALI/ARDS中特定作用方面的差距，并概述了TGF依赖性调节炎症性肺损伤和血管修复领域未来的研究方向。已在ALI/ARDS发病机制和肺纤维化中研究了TGFs的功能作用，大多数研究表明TGF-β1具有促损伤和促纤维化作用。研究还表明，TGF-α与炎症性肺损伤和纤维化呈正相关。然而，TGF-β2和TGF-β3对ALI/ARDS的作用尚不清楚，并且所有TGF异构体对ALI/ARDS后血管修复的作用也未得到充分表征。更好地理解TGFs对炎症性肺损伤和修复的调节作用可能会为ALI/ARDS患者开发出一种安全有效的治疗策略。
