Abstract
Objectives
Hyaluronic acid (HA), a large non-sulfated glycosaminoglycan, is one of the major components of extracellular matrix (ECM) in connective tissues and other organs. Currently, it is widely used as a dietary supplement, especially for treatment or prevention of aging-related disorders. On the other hand, HA has been reported with an increased risk of kidney stone disease, particularly calcium oxalate (CaOx) type, but with unclear mechanisms. We therefore performed systematic analyses for its modulatory effects on CaOx monohydrate (COM) crystal at various steps of kidney stone formation processes.
Methods
HA at 1, 10, 100, 1000 and 10,000 ng/ml was tested in various assays for COM crystallization, crystal growth, aggregation, crystal-cell adhesion and invasion through ECM.
Results
COM crystallization and crystal aggregation were not affected by HA at all concentrations. However, HA significantly promoted COM crystal growth and adhesion onto renal tubular cells in a dose-dependent manner. Interestingly, COM crystal invasion through the ECM was dramatically enhanced by HA even at very low concentration (such as 1 ng/ml).
Conclusions
Our findings provide evidence for promoting effects of HA on COM crystal growth, adhesion on renal tubular cell surface and invasion through the ECM, all of which are the important steps for kidney stone formation.
Funding Sources
TRF-IRN grant.
Dual modulatory effects of diosmin on calcium oxalate kidney stone formation processes: Crystallization, growth, aggregation, crystal-cell adhesion, internalization into renal tubular cells, and invasion through extracellular matrix
