Park Cheol Ho, Yoo Tae-Hyun
Department of Internal Medicine, Institute of Kidney Disease Research, College of Medicine, Yonsei University, Seodaemun-gu, Seoul 03722, Republic of Korea.
Pharmaceuticals (Basel). 2022 Nov 29;15(12):1485. doi: 10.3390/ph15121485.
Kidney fibrosis is a common pathophysiological mechanism of chronic kidney disease (CKD) progression caused by several underlying kidney diseases. Among various contributors to kidney fibrosis, transforming growth factor-β1 (TGF-β1) is the major factor driving fibrosis. TGF-β1 exerts its profibrotic attributes via the activation of canonical and non-canonical signaling pathways, which induce proliferation and activation of myofibroblasts and subsequent accumulation of extracellular matrix. Over the past few decades, studies have determined the TGF-β1 signaling pathway inhibitors and evaluated whether they could ameliorate the progression of CKD by hindering kidney fibrosis. However, therapeutic strategies that block TGF-β1 signaling have usually demonstrated unsatisfactory results. Herein, we discuss the therapeutic concepts of the TGF-β1 signaling pathway and its inhibitors and review the current state of the art regarding regarding TGF-β1 inhibitors in CKD management.
肾纤维化是由多种潜在肾脏疾病引起的慢性肾脏病（CKD）进展的常见病理生理机制。在导致肾纤维化的各种因素中，转化生长因子-β1（TGF-β1）是驱动纤维化的主要因素。TGF-β1通过激活经典和非经典信号通路发挥其促纤维化特性，这些信号通路诱导肌成纤维细胞的增殖和激活以及随后细胞外基质的积累。在过去几十年中，研究已经确定了TGF-β1信号通路抑制剂，并评估了它们是否可以通过抑制肾纤维化来改善CKD的进展。然而，阻断TGF-β1信号的治疗策略通常显示出不尽人意的结果。在此，我们讨论TGF-β1信号通路及其抑制剂的治疗概念，并回顾CKD管理中TGF-β1抑制剂的当前研究现状。
