Abstract
To investigate how organic anion transporter (OAT)-1 is involved in uric acid nephropathy (UAN), a rat model for UAN was established and the serum uric acid, blood urea nitrogen and serum creatinine levels were all measured, and observed to be increased. It was additionally identified that in UAN rats the surface OAT1 expression levels were reduced. By treating HEK cells with monosodium urate (MSU) crystals, it was observed that the cells exhibited a reduction in OAT1 levels. Furthermore, MSU crystals were observed to recruit Ras homolog family member A (RhoA), a small guanosine triphosphatase, to the membrane and activate it. Following RhoA activation, the OAT1 internalization rate was identified to be increased. The dominant-negative RhoA N19 mutation was able to block MSU-induced OAT1 internalization, indicating that the process was RhoA-dependent. Finally, the results indicated that folic acid, a daily nutritional supplement, was capable of rescuing MSU-induced nephropathy and OAT1 internalization. These observations indicated that uric acid crystals were able to reduce the OAT1 membrane distribution through activating RhoA, and that folic acid was capable of preventing MSU-induced OAT1 relocation by inhibiting the RhoA signaling pathway.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
