AUTHOR=Wang Yanzhe , Wu Ming , Yang Feng , Lin Junyan , Zhang Li , Yuan Meijie , Chen Dongping , Tan Bo , Huang Di , Ye Chaoyang 

TITLE=Protein arginine methyltransferase 3 inhibits renal tubulointerstitial fibrosis through asymmetric dimethylarginine

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.995917

DOI=10.3389/fmed.2022.995917

ISSN=2296-858X

ABSTRACT=<p>Mammalian protein arginine methyltransferase 3 (PRMT3) catalyzes the monomethylation and dimethylation of the arginine residues of proteins. The role of PRMT3 in renal fibrosis is currently unknown. We aimed to study the role of PRMT3 in renal fibrosis and explored its underlying mechanisms. Quantitative PCR analysis and Western blotting analysis showed that the expression of PRMT3 was up-regulated in unilateral ureteral obstruction (UUO) mouse kidneys. Knockout of <italic>Prmt3</italic> gene enhanced interstitial fibrosis in UUO kidneys as shown by Masson staining and Western blotting analysis the expression of pro-fibrotic markers. The production of asymmetric dimethylarginine (ADMA) was increased in wide type UUO kidneys but not further increased in <italic>Prmt3</italic> knockout UUO kidneys. Administration of exogeneous ADMA in UUO kidneys blocked the enhanced renal interstitial fibrosis in <italic>Prmt3</italic> mutant mice. Moreover, genetic deletion of <italic>Prmt3</italic> gene increased blood urea nitrogen levels and renal deposition of collagen in folic acid injected mice. We conclude that PRMT3 inhibits renal tubulointerstitial fibrosis through elevating renal ADMA levels.</p>