title: Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy.
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.
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Xinlin
authors: X
authors: Wu
authors: Key Laboratory of Medicinal Biotechnology, Guilin Medical University, Guilin, Guangxi 541004, P.R. China.
authors: Jianxiang
authors: J
authors: Liu
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Jianqing
authors: J
authors: Zhang
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Heng
authors: H
authors: Liu
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Miansheng
authors: M
authors: Yan
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Birong
authors: B
authors: Liang
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Hongbo
authors: H
authors: Xie
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Shijun
authors: S
authors: Zhang
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Baoguo
authors: B
authors: Sun
authors: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors: Houming
authors: H
authors: Zhou
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003460:Crystallization; D004195:Disease Models, Animal; D004705:Endocytosis / Q000187:drug effects*; D005492:Folic Acid / Q000494:pharmacology*; D007674:Kidney Diseases / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism*; D021381:Protein Transport; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D027362:Organic Anion Transport Protein 1; C421043:Slc22a6 protein, rat; D014527:Uric Acid; D005492:Folic Acid; D020742:rhoA GTP-Binding Protein