The hyaluronan (HA) matrix in the tissue microenvironment is crucial for maintaining homeostasis by regulating inflammatory signalling, endothelial–mesenchymal transition and cell migration. During development, covalent modifications and osmotic swelling of HA create mechanical forces that initiate midgut rotation, vascular patterning and branching morphogenesis. Together with its main cell surface receptor, CD44, HA establishes a physicochemical scaffold at the cell surface that facilitates the interaction and clustering of growth factors and receptors that is required for normal physiology. High-molecular-weight HA, tumour necrosis factor-stimulated gene 6, pentraxin 3 and CD44 form a stable pericellular matrix that promotes tissue regeneration and reduces inflammation. By contrast, breakdown of high-molecular-weight HA into depolymerized fragments by hyaluronidases triggers inflammatory signalling, leukocyte migration and angiogenesis, contributing to tissue damage and fibrosis in kidney disease. Targeting HA metabolism is challenging owing to its dynamic regulation and tissue-specific functions. Nonetheless, modulating HA matrix functions by targeting its binding partners holds promise as a therapeutic strategy for restoring tissue homeostasis and mitigating pathological processes. Further research in this area is warranted to enable the development of novel therapeutic approaches for kidney and other diseases characterized by dysregulated HA metabolism.

组织微环境中的透明质酸 （HA） 基质通过调节炎症信号传导、内皮-间充质转化和细胞迁移，对于维持体内平衡至关重要。在发育过程中，HA 的共价修饰和渗透性膨胀会产生机械力，从而启动中肠旋转、血管模式和分支形态发生。HA 与其主要的细胞表面受体 CD44 一起在细胞表面建立了一个物理化学支架，促进正常生理学所需的生长因子和受体的相互作用和聚集。高分子量 HA、肿瘤坏死因子刺激基因 6、五聚蛋白 3 和 CD44 形成稳定的细胞周基质，促进组织再生并减少炎症。相比之下，透明质酸酶将高分子量 HA 分解成解聚片段会触发炎症信号、白细胞迁移和血管生成，从而导致肾脏疾病的组织损伤和纤维化。由于其动态调节和组织特异性功能，靶向 HA 代谢具有挑战性。尽管如此，通过靶向其结合伴侣来调节 HA 基质功能有望成为恢复组织稳态和缓解病理过程的治疗策略。该领域的进一步研究是必要的，以便能够开发新的治疗方法，用于治疗肾脏和其他以 HA 代谢失调为特征的疾病。