Renal fibrosis is a major factor in the progression of chronic kidney disease and the final common pathway of kidney injury. Therefore, the effective therapies against renal fibrosis are urgently needed. The objective of this study was to investigate the effect of Am80, a synthetic retinoic acid receptor (RAR) agonist, in the treatment of renal interstitial fibrosis using unilateral ureteral obstruction (UUO) mice. The findings indicate that Am80 treatment suppressed renal fibrosis and inflammation to the same degree as the naturally-occuring retinoic acid, all-trans retinoic acid (atRA). But the adverse effect of body weight loss in Am80-treated mice was lower compared to the atRA treatment. The hepatic mRNA levels of alpha-1-acid glycoprotein (AGP), a downstream molecule of RAR agonist, was increased following administration of Am80 to healthy mice. In addition, increased AGP mRNA expression was also observed in HepG2 cells and THP-1-derived macrophages that had been treated with Am80. AGP-knockout mice exacerbated renal fibrosis, inflammation and macrophage infiltration in UUO mice, indicating endogenous AGP played an anti-fibrotic and anti-inflammatory role during the development of renal fibrosis. We also found that no anti-fibrotic effect of Am80 was observed in UUO-treated AGP-knockout mice whereas atRA treatment tended to show a partial anti-fibrotic effect. These collective findings suggest that Am80 protects against renal fibrosis via being involved in AGP function.

肾纤维化是慢性肾脏病进展的主要因素，也是肾损伤的最终共同途径。因此，迫切需要针对肾纤维化的有效治疗方法。本研究的目的是利用单侧输尿管梗阻 (UUO) 小鼠研究 Am80（一种合成视黄酸受体 (RAR) 激动剂）治疗肾间质纤维化的效果。研究结果表明，Am80 治疗抑制肾纤维化和炎症的程度与天然存在的视黄酸、全反式视黄酸 (atRA) 相同。但与 atRA 治疗相比，Am80 治疗小鼠体重减轻的不利影响较低。健康小鼠服用 Am80 后，RAR 激动剂下游分子 α1-酸性糖蛋白 (AGP) 的肝脏 mRNA 水平增加。此外，在用 Am80 处理的 HepG2 细胞和 THP-1 衍生的巨噬细胞中也观察到 AGP mRNA 表达增加。 AGP敲除小鼠加剧了UUO小鼠的肾纤维化、炎症和巨噬细胞浸润，表明内源性AGP在肾纤维化的发展过程中发挥了抗纤维化和抗炎作用。我们还发现，在 UUO 治疗的 AGP 敲除小鼠中没有观察到 Am80 的抗纤维化作用，而 atRA 治疗往往显示出部分抗纤维化作用。这些共同发现表明 Am80 通过参与 AGP 功能来预防肾纤维化。