Abstract:
Renal fibrosis (RF) is one of the underlying pathological conditions leading to progressive loss of renal function and end-stage renal disease (ESRD). Over the years, various therapeutic approaches have been explored to combat RF and prevent ESRD. Despite significant advances in understanding the underlying molecular mechanism(s), effective therapeutic interventions for RF are limited. Current therapeutic strategies primarily target these underlying mechanisms to halt or reverse fibrotic progression. Inhibition of transforming growth factor-β (TGF-β) signaling, a pivotal mediator of RF has emerged as a central strategy to manage RF. Small molecules, peptides, and monoclonal antibodies that target TGF-β receptors or downstream effectors have demonstrated potential in preclinical models. Modulating the renin-angiotensin system and targeting the endothelin system also provide established approaches for controlling fibrosis-related hemodynamic changes. Complementary to pharmacological strategies, lifestyle modifications, and dietary interventions contribute to holistic management. This comprehensive review aims to summarize the underlying mechanisms of RF and provide an overview of the therapeutic strategies and novel antifibrotic agents that hold promise in its treatment.
摘要:
肾纤维化(RF)是导致肾功能进行性丧失和终末期肾病(ESRD)的潜在病理状况之一。多年来,已经探索了各种治疗方法来对抗RF和预防ESRD。尽管在理解潜在的分子机制方面取得了重大进展,RF的有效治疗干预措施是有限的。目前的治疗策略主要针对这些潜在机制以阻止或逆转纤维化进展。抑制转化生长因子-β(TGF-β)信号,RF的关键中介已成为管理RF的中心策略。小分子,肽,和靶向TGF-β受体或下游效应物的单克隆抗体已在临床前模型中证明了潜力。调节肾素-血管紧张素系统和靶向内皮素系统也提供了控制纤维化相关血液动力学变化的既定方法。补充药理学策略,改变生活方式,和饮食干预有助于整体管理。这篇全面的综述旨在总结RF的潜在机制,并概述治疗策略和新型抗纤维化药物在其治疗中的应用前景。