Yang Fan, Cheng Ming-Han, Pan Hai-Feng, Gao Jian
Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China.
Department of Ophthalmology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Acta Pharm Sin B. 2024 Aug;14(8):3312-3326. doi: 10.1016/j.apsb.2024.04.026. Epub 2024 May 6.
Progranulin (PGRN), a multifunctional growth factor-like protein expressed by a variety of cell types, serves an important function in the physiologic and pathologic processes of fibrotic diseases, including wound healing and the inflammatory response. PGRN was discovered to inhibit pro-inflammation effect by competing with tumor necrosis factor-alpha (TNF-) binding to TNF receptors. Notably, excessive tissue repair in the development of inflammation causes tissue fibrosis. Previous investigations have indicated the significance of PGRN in regulating inflammatory responses. Recently, multiple studies have shown that PGRN was linked to fibrogenesis, and was considered to monitor the formation of fibrosis in multiple organs, including liver, cardiovascular, lung and skin. This paper is a comprehensive review summarizing our current knowledge of PGRN, from its discovery to the role in fibrosis. This is followed by an in-depth look at the characteristics of PGRN, consisting of its structure, basic function and intracellular signaling. Finally, we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.
颗粒蛋白前体（PGRN）是一种由多种细胞类型表达的多功能生长因子样蛋白，在纤维化疾病的生理和病理过程中发挥重要作用，包括伤口愈合和炎症反应。研究发现，PGRN通过与肿瘤坏死因子-α（TNF-α）竞争结合TNF受体来抑制促炎作用。值得注意的是，炎症发展过程中过度的组织修复会导致组织纤维化。先前的研究表明PGRN在调节炎症反应方面具有重要意义。最近，多项研究表明PGRN与纤维生成有关，并被认为可监测包括肝脏、心血管、肺和皮肤在内的多个器官中的纤维化形成。本文是一篇全面综述，总结了我们目前对PGRN的认识，从其发现到在纤维化中的作用。接下来将深入探讨PGRN的特征，包括其结构、基本功能和细胞内信号传导。最后，我们将讨论PGRN在纤维化诊断和治疗中的潜力。
