ABSTRACT

Introduction: Hepatic stellate cells (HSCs) are essential for physiological homeostasis of the liver extracellular matrix (ECM). Excessive transdifferentiation of HSC from a quiescent to an activated phenotype contributes to disrupt this balance and can lead to liver fibrosis. Accumulating evidence has suggested that nuclear receptors (NRs) are involved in the regulation of HSC activation, proliferation, and function. Therefore, these NRs may be therapeutic targets to balance ECM homeostasis and inhibit HSC activation in liver fibrosis.

Areas covered: In this review, the authors summarized the recent progress in the understanding of the regulatory role of NRs in HSCs and their potential as drug targets in liver fibrosis.

Expert opinion: NRs are still potential therapy targets for inhibiting HSCs activation and liver fibrosis. However, the development of NRs agonists or antagonists to inhibit HSCs requires fully consideration of systemic effects.

摘要

简介： 肝星状细胞 (HSC) 对于肝细胞外基质 (ECM) 的生理稳态至关重要。HSC 从静止表型到激活表型的过度转分化会破坏这种平衡，并可能导致肝纤维化。越来越多的证据表明，核受体 (NRs) 参与 HSC 激活、增殖和功能的调节。因此，这些 NRs 可能是平衡 ECM 稳态和抑制肝纤维化中 HSC 激活的治疗靶点。

涵盖的领域：在这篇综述中，作者总结了在理解 NRs 在 HSC 中的调节作用及其作为肝纤维化药物靶点的潜力方面的最新进展。

专家意见：NRs 仍然是抑制 HSCs 活化和肝纤维化的潜在治疗靶点。然而，开发 NRs 激动剂或拮抗剂来抑制 HSCs 需要充分考虑全身效应。