Rooney Peadar, Srivastava Akshay, Watson Luke, Quinlan Leo R, Pandit Abhay
Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
Physiology School of Medicine, National University of Ireland, Galway, Ireland.
Acta Biomater. 2015 Jun;19:66-75. doi: 10.1016/j.actbio.2015.02.030. Epub 2015 Mar 26.
Hyaluronic acid (HA) has received a lot of attention recently as a biomaterial with applications in wound healing, drug delivery, vascular repair and cell and/or gene delivery. Interstitial cystitis (IC) is characterised by an increase in the permeability of the bladder wall urothelium due to loss of the glycosaminoglycan (GAG) layer. The degradation of the urothelium leads to chronic pain and urinary dysfunction. The aetiology of the degradation of the GAG layer in this instance is currently unknown. At a clinical level, GAG replacement therapy using a HA solution is currently utilised as a treatment for IC. However, there is a significant lack of data on the mechanism of action of HA in IC. The current study investigates the mechanistic effect of clinically relevant HA treatment on an in vitro model of IC using urothelial cells, examining cytokine secretion, GAG secretion and trans-epithelial permeability. This study demonstrates that HA can significantly decrease induced cytokine secretion (4-5 fold increase), increase sulphated GAG production (2-fold increase) and without altering tight junction expression, decrease trans-epithelial permeability, suggesting that the HA pathway is a clinical target and potential treatment vector.
透明质酸（HA）作为一种生物材料，在伤口愈合、药物递送、血管修复以及细胞和/或基因递送等方面有应用，最近受到了广泛关注。间质性膀胱炎（IC）的特征是膀胱壁尿路上皮的通透性增加，这是由于糖胺聚糖（GAG）层的缺失所致。尿路上皮的降解会导致慢性疼痛和排尿功能障碍。在这种情况下，GAG层降解的病因目前尚不清楚。在临床层面，目前使用HA溶液进行GAG替代疗法来治疗IC。然而，关于HA在IC中的作用机制，数据非常缺乏。当前的研究使用尿路上皮细胞，在IC的体外模型中研究了临床相关HA治疗的作用机制，检测了细胞因子分泌、GAG分泌和跨上皮通透性。这项研究表明，HA可以显著降低诱导的细胞因子分泌（增加4 - 5倍），增加硫酸化GAG的产生（增加2倍），并且在不改变紧密连接表达的情况下，降低跨上皮通透性，这表明HA途径是一个临床靶点和潜在的治疗载体。
