Hu Yuchen, Peng Linrui, Zhuo Xinyu, Yang Chan, Zhang Yuwei
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu 610041, China.
Biomolecules. 2024 Nov 22;14(12):1485. doi: 10.3390/biom14121485.
Hedgehog (Hh) signaling is a well-established developmental pathway; it is crucial for early embryogenesis, cell differentiation, and damage-driven regeneration. It is being increasingly recognized that dysregulated Hh signaling is also involved in fibrotic diseases, which are characterized by excessive extracellular matrix deposition that compromises tissue architecture and function. As in-depth insights into the mechanisms of Hh signaling are obtained, its complex involvement in fibrosis is gradually being illuminated. Notably, some Hh-targeted inhibitors are currently under exploration in preclinical and clinical trials as a means to prevent fibrosis progression. In this review, we provide a concise overview of the biological mechanisms involved in Hh signaling. We summarize the latest advances in our understanding of the roles of Hh signaling in fibrogenesis across the liver, kidneys, airways, and lungs, as well as other tissues and organs, with an emphasis on both the shared features and, more critically, the distinct functional variations observed across these tissues and organs. We thus highlight the context dependence of Hh signaling, as well as discuss the current status and the challenges of Hh-targeted therapies for fibrosis.
刺猬信号通路（Hh信号通路）是一条已被充分证实的发育通路；它对早期胚胎发育、细胞分化以及损伤驱动的再生至关重要。人们越来越认识到，Hh信号通路失调也与纤维化疾病有关，这些疾病的特征是细胞外基质过度沉积，从而损害组织结构和功能。随着对Hh信号通路机制的深入了解，其在纤维化中的复杂作用逐渐明晰。值得注意的是，目前一些针对Hh的抑制剂正在进行临床前和临床试验，作为预防纤维化进展的一种手段。在这篇综述中，我们简要概述了Hh信号通路涉及的生物学机制。我们总结了对Hh信号通路在肝脏、肾脏、气道和肺以及其他组织和器官的纤维化形成中作用的最新认识进展，重点关注这些组织和器官中共同的特征，更关键的是，关注观察到的不同功能差异。因此，我们强调了Hh信号通路的背景依赖性，并讨论了针对纤维化的Hh靶向治疗的现状和挑战。
