Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis.
Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis.
复制标题
DOI：
10.12701/yujm.2020.00458
复制
发表时间：
2020-10
影响因子：
--
通讯作者：
Woo CH
中科院分区：
文献类型：
--
作者：
Kim S;Lim JH;Woo CH
纤维化的特征是细胞外基质成分过度积累。纤维化过程最终导致肺纤维化、晚期肾病和肝硬化等慢性炎症和代谢疾病的器官功能障碍和衰竭。特发性肺纤维化（IPF）是一种病因不明的进行性慢性间质性肺疾病的常见形式。从病理生理学角度来看，肺泡、间质和毛细血管内皮的实质变得疤痕和僵硬，这使得呼吸困难，因为肺部必须更加努力地在肺泡腔和血液之间转移氧气和二氧化碳。转化生长因子β（TGF-β）信号通路在肺纤维化和肺组织瘢痕形成的发病机制中发挥重要作用。最近的临床试验集中于开发直接或间接靶向激酶来治疗 IPF 的药物。因此，为了开发肺纤维化的治疗靶点，有必要了解肺纤维化发病机制的关键因素及其潜在的信号通路。本综述的目的是讨论激酶信号级联在 TGF-β 依赖性或其他信号通路的调节中的作用，包括 Rho 相关卷曲螺旋激酶、c-jun N 末端激酶、细胞外信号调节激酶 5 和 p90 核糖体 S6 激酶通路，以及 IPF 的潜在治疗靶点。
Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.