Soluble biglycan, a small leucine-rich proteoglycan, plays a significant role in several pathologies as it has emerged as an extracellular matrix-derived danger-associated molecular pattern. Biglycan is released from the extracellular matrix in response to tissue injury and, as a canonical danger signal, interacts with innate immune receptors, Toll-like receptors 2 and 4, thereby triggering a sustained inflammatory response. Recent evidence indicates that biglycan acts as a molecular switch between inflammation and autophagy by a specific interaction with the Toll-like co-receptor CD14 and CD44, respectively. Biglycan-evoked autophagy further contributes to the anti-inflammatory M2 macrophage polarization, inflammation resolution and tissue repair. These multivalent roles of soluble biglycan have been well characterized in inflammatory kidney diseases. In chronic liver diseases, increased levels of soluble biglycan have been described for years, leading to utilization of biglycan serum levels as a non-invasive biomarker for fibrosis. Hepatorenal dysfunction represents a classic example of inter-organ crosstalk, in which functional and molecular alterations of the cirrhotic liver can promote the development of renal failure. In patients with liver cirrhosis, development of hepatorenal syndrome is associated with high mortality. In this review, we will discuss the crucial role of soluble biglycan in inflammation and autophagy and its possible implications for hepatorenal dysfunction. We propose a novel concept of hepatorenal crosstalk, that is, biglycan produced by the cirrhotic liver could constitute a circulating “messenger” for the kidneys triggering inflammation and/or autophagy ultimately affecting disease outcome.

可溶性双糖链蛋白聚糖是一种富含亮氨酸的小蛋白聚糖，在多种病理学中发挥着重要作用，因为它已成为细胞外基质衍生的危险相关分子模式。Biglycan 在组织损伤时从细胞外基质中释放出来，作为典型的危险信号，它与先天免疫受体 Toll 样受体 2 和 4 相互作用，从而引发持续的炎症反应。最近的证据表明，双糖链蛋白聚糖通过分别与 Toll 样共受体 CD14 和 CD44 的特异性相互作用充当炎症和自噬之间的分子开关。Biglycan 诱发的自噬进一步有助于抗炎 M2 巨噬细胞极化、炎症消退和组织修复。可溶性双糖链蛋白聚糖的这些多价作用已在炎症性肾病中得到很好的表征。在慢性肝病中，可溶性双糖链蛋白聚糖的水平已被描述多年，导致血清双糖链蛋白聚糖水平被用作纤维化的非侵入性生物标志物。肝肾功能障碍代表了器官间串扰的典型例子，其中肝硬化的功能和分子改变可以促进肾功能衰竭的发展。在肝硬化患者中，肝肾综合征的发展与高死亡率相关。在这篇综述中，我们将讨论可溶性双糖链蛋白聚糖在炎症和自噬中的关键作用及其对肝肾功能障碍的可能影响。我们提出了一个新的肝肾串扰概念，即