The aim of this study was to explore the contribution and the mechanism of uric acid (UA) to phenotypic change in rat glomerular mesangial cells.Methods
Rat glomerular mesangial cells (HBZY-1) were exposed to UA (0.05 mmol/L to 0.4 mmol/L) for 24 h to 48 h. Subsequently, 4-phenyl butyric acid (4-PBA) (5 mg/dL) was added and 48 h incubation was performed. HBZY-1 cells exposed to UA (0.4 mmol/L) were incubated for 48 h. After incubation, the cells were examined under an inverted microscope and transmission electron microscope to observe their morphologies and the expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), fibronectin (FN), glucose regulated protein 78 (GRP78), and the protein disulfide isomerase (PDI) proteins and mRNA in the HBZY-1 cells were measured by Western blot and reversed transcription-polymerase chain reaction.Results
HBZY-1 cultured in UA showed evident morphological changes under transmission electron microscopy. The soluble UA stimulated the upregulation of the α-SMA, TGF-β1 and FN mRNA and proteins in a concentration- and time-dependent manner. UA-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulation of the mRNA and protein expressions of GRP78 and PDI. However, the upregulation was reverted by 4-PBA, an inhibitor of ER stress.Conclusions
Uric acid induces phenotypic change in HBZY-1 cells. ER stress plays a central role in UA-induced phenotypic transformation in vitro. 4-PBA may be beneficial in attenuating UA-induced glomerular injury.Summary at a Glance
Hyperuricaemia plays a role in the progression of renal disease where uric acid (UA) induces deleterious effects on glomerular cells. Li et al. report that rat glomerular mesangial cells exposed to UA show morphological and phenotypic changes in vitro. Furthermore, UA induced endoplasmic reticular (ER) stress as indicated by an upregulated expression of glucose regulated protein 78 (GR78) and protein disulphide isomerase (PDI) at the protein and mRNA level.