Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, Viale dei Cappuccini, 1, San Giovanni Rotondo, FG, Italy.
Institute for Liver and Digestive Health, Royal Free Hospital, University College London (UCL), London, UK.
Clin Exp Med. 2017 Aug;17(3):269-280. doi: 10.1007/s10238-016-0438-x. Epub 2016 Sep 21.
Hepatic stellate cells (HSCs), also known as perisinusoidal cells, are pericytes found in the perisinusoidal space of the liver. HSCs are the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. When the liver is damaged, stellate cells can shift into an activated state, characterized by proliferation, contractility and chemotaxis. The activated HSCs secrete collagen scar tissue, which can lead to cirrhosis. Recent studies have shown that in vivo activation of HSCs by fibrogenic agents can eventually lead to senescence of these cells, which would contribute to reversal of fibrosis although it may also favor the insurgence of liver cancer. HSCs in their non-active form store huge amounts of retinoic acid derivatives in lipid droplets, which are progressively depleted upon cell activation in injured liver. Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, generally required for growth and development. The precise function of retinoic acid and its alterations in HSCs has yet to be elucidated, and nonetheless in various cell types retinoic acid and its receptors (RAR and RXR) are known to act synergistically with peroxisome proliferator-activated receptor gamma (PPAR-gamma) signaling through the activity of transcriptional heterodimers. Here, we review the recent advancements in the understanding of how retinoic acid signaling modulates the fibrogenic potential of HSCs and proposes a synergistic combined action with PPAR-gamma in the reversal of liver fibrosis.
肝星状细胞（HSCs），也称为窦周细胞，是存在于肝脏窦周间隙的周细胞。HSCs 是肝纤维化过程中主要涉及的细胞类型，肝纤维化是肝脏损伤后形成疤痕组织的过程。当肝脏受损时，星状细胞可以转变为激活状态，其特征为增殖、收缩和趋化性。激活的 HSCs 分泌胶原疤痕组织，可导致肝硬化。最近的研究表明，纤维生成剂在体内激活 HSCs 最终可导致这些细胞衰老，尽管这可能有利于肝癌的发生，但也有助于逆转纤维化。处于非激活状态的 HSCs 在脂滴中储存大量视黄酸衍生物，这些衍生物在受损肝脏中细胞激活时逐渐耗尽。视黄酸是维生素 A（视黄醇）的代谢产物，可介导维生素 A 的功能，通常需要生长和发育。视黄酸及其在 HSCs 中的变化的确切功能尚未阐明，但在各种细胞类型中，视黄酸及其受体（RAR 和 RXR）与过氧化物酶体增殖物激活受体γ（PPAR-γ）信号协同作用，通过转录异二聚体的活性。在这里，我们综述了对视黄酸信号如何调节 HSCs 的纤维化潜能的理解的最新进展，并提出了与 PPAR-γ在逆转肝纤维化中的协同联合作用。
