Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Hepatol Commun. 2023 Mar 17;7(4). doi: 10.1097/HC9.0000000000000083. eCollection 2023 Apr 1.
Hyaluronan (HA), also known as hyaluronic acid, is a glycosaminoglycan that is a critical component of the extracellular matrix (ECM). Production and deposition of ECM is a wound-healing response that occurs during chronic liver disease, such as cirrhosis. ECM production is a sign of the disease progression of fibrosis. Indeed, the accumulation of HA in the liver and elevated serum HA levels are used as biomarkers of cirrhosis. However, recent studies also suggest that the ECM, and HA in particular, as a functional signaling molecule, facilitates disease progression and regulation. The systemic and local levels of HA are regulated by de novo synthesis, cleavage, endocytosis, and degradation of HA, and the molecular mass of HA influences its pathophysiological effects. However, the regulatory mechanisms of HA synthesis and catabolism and the functional role of HA are still poorly understood in liver fibrosis. This review summarizes the role of HA in liver fibrosis at molecular levels as well as its clinical implications and discusses the potential therapeutic uses of targeting HA in liver fibrosis.
透明质酸（HA），也称为透明质酸，是一种糖胺聚糖，是细胞外基质（ECM）的重要组成部分。ECM 的产生和沉积是慢性肝病（如肝硬化）过程中发生的伤口愈合反应。ECM 的产生是纤维化疾病进展的标志。事实上，HA 在肝脏中的积累和血清中 HA 水平的升高被用作肝硬化的生物标志物。然而，最近的研究还表明，ECM，特别是 HA，作为一种功能性信号分子，促进疾病的进展和调控。HA 的系统性和局部水平受到 HA 的从头合成、裂解、内吞作用和降解的调节，HA 的分子量影响其病理生理作用。然而，HA 合成和分解代谢的调节机制以及 HA 的功能作用在肝纤维化中仍知之甚少。这篇综述总结了 HA 在肝纤维化中的分子水平作用及其临床意义，并讨论了靶向 HA 治疗肝纤维化的潜在治疗用途。
