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αv整合素抑制在纤维化肺病和癌症发生中的治疗前景

Therapeutic Prospects of αv Integrins Inhibition in Fibrotic Lung Diseases and Carcinogenesis.

作者信息

Golovina Eugenija Leonidovna, Kochubey Veronika Vladimirovna, Shabanova Marina Alekseevna, Chekhvalova Darya Maksimovna, Serebryakova Valentina Alexandrovna, Skurikhin Evgenii Germanovich, Vaizova Olga Evgenievna, Morozov Sergey Georgievich, Kubatiev Aslan Amirkhanovich, Dygai Alexander Mikhaylovich

机构信息

Department of Pharmacology, Siberian State Medical University, Ministry of Health of the Russian Federation, Tomsk 634050, Russia.

Laboratory of Regulation of Reparative Processes, Institute of General Pathology and Pathophysiology, Moscow 125315, Russia.

出版信息

Int J Mol Sci. 2025 Jun 27;26(13):6202. doi: 10.3390/ijms26136202.

Abstract

The uncontrolled fibrosis of lung tissue can lead to premature death in patients suffering from idiopathic pulmonary fibrosis (IPF), and it complicates the course of chronic obstructive pulmonary disease (COPD) and emphysema. It is also a risk factor for developing lung cancer. Antifibrotic drugs, such as nantedanib and pirfenidone, are able to slow down the progression of pulmonary fibrosis, but more effective treatment is still needed to reverse it. Studies on the pathogenesis of tissue fibrosis have demonstrated that integrins play a crucial role affecting the development of pulmonary fibrosis, for example, by activating transforming growth factor-β (TGF-β). Taking the above into consideration, targeting specific integrins could offer promising opportunities for managing fibroplastic changes in lung tissue. Integrins are a type of transmembrane molecule that mediate interactions between cells and extracellular matrix (ECM) molecules. This review discusses the role of integrins in the pathogeneses of respiratory diseases and carcinogenesis, as well as presents promising approaches to the drug therapy of pulmonary fibrosis of various etiologies based on integrin inhibition.

摘要

肺组织的不受控制的纤维化可导致特发性肺纤维化(IPF)患者过早死亡,并且它会使慢性阻塞性肺疾病(COPD)和肺气肿的病程复杂化。它也是患肺癌的一个风险因素。抗纤维化药物,如尼达尼布和吡非尼酮,能够减缓肺纤维化的进展,但仍需要更有效的治疗来逆转它。对组织纤维化发病机制的研究表明,整合素发挥着关键作用,例如通过激活转化生长因子-β(TGF-β)来影响肺纤维化的发展。考虑到上述情况,靶向特定整合素可能为控制肺组织的纤维增生性变化提供有前景的机会。整合素是一类介导细胞与细胞外基质(ECM)分子之间相互作用的跨膜分子。本综述讨论了整合素在呼吸系统疾病发病机制和致癌过程中的作用,并介绍了基于整合素抑制的针对各种病因的肺纤维化药物治疗的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c9f/12249868/21403ba2af8b/ijms-26-06202-g001.jpg

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