Relaxin (RLX) is a heterodimeric, polypeptide hormone that has natural anti-fibrotic activity in many organs. During the chronic liver injury, hepatic stellate cells (HSCs) are phenotypically transformed into myofibroblasts. This process is known as activation of HSCs. Activated HSCs play a central role in hepatic fibrosis. Quiescent HSCs were shown to express low levels of RLX receptors such as RXFP1 and RXFP2. Upon chronic liver injury, HSCs are activated and express high levels of the RLX receptors. ML290, an agonist of RXFP1 has been reported to have antifibrotic effect in vitro as well as in vivo. Serelaxin, a recombinant human RLX-2 treatment has reduced hepatic fibrosis and portal hypertension in experimental models due to its vasodilation properties by inducing intrahepatic nitric oxide level. Serelaxin has also produced a neutral effect when studied against human cirrhosis-related portal hypertension in clinical trials. RLX is a potent collagen synthesis inhibitor and it has extracellular matrix (ECM) remodeling properties by promoting matrix metalloproteinases and downregulating expression of metalloproteinases inhibitors. Available reports suggest that RLX could induce ECM remodeling and suppress the profibrogenic transforming growth factor-β signaling and thereby regress hepatic fibrosis. Though RLX has natural antifibrotic activity, its antifibrotic molecular mechanisms especially in hepatic fibrosis condition are not reported. This review exclusively focuses antifibrotic effect of RLX on hepatic fibrosis.

松弛素 (RLX) 是一种异二聚体多肽激素，在许多器官中具有天然的抗纤维化活性。在慢性肝损伤期间，肝星状细胞 (HSC) 在表型上转化为肌成纤维细胞。这个过程被称为 HSC 的激活。活化的 HSC 在肝纤维化中起核心作用。静止的 HSC 显示低水平的 RLX 受体，如 RXFP1 和 RXFP2。慢性肝损伤后，HSC 被激活并表达高水平的 RLX 受体。ML290 是 RXFP1 的一种激动剂，据报道在体外和体内都具有抗纤维化作用。Serelaxin 是一种重组人 RLX-2 治疗药物，由于其通过诱导肝内一氧化氮水平的血管舒张特性，在实验模型中减少了肝纤维化和门静脉高压症。在临床试验中针对人类肝硬化相关的门静脉高压症进行研究时，Serelax 也产生了中性作用。RLX 是一种有效的胶原蛋白合成抑制剂，它通过促进基质金属蛋白酶和下调金属蛋白酶抑制剂的表达而具有细胞外基质 (ECM) 重塑特性。现有报告表明，RLX 可以诱导 ECM 重塑并抑制促纤维化转化生长因子-β 信号传导，从而使肝纤维化消退。尽管 RLX 具有天然的抗纤维化活性，但其抗纤维化分子机制，尤其是在肝纤维化条件下的抗纤维化分子机制尚未见报道。