AUTHOR=Zhu Zewu , Huang Fang , Xia Weiping , Zeng Huimin , Gao Meng , Li Yongchao , Zeng Feng , He Cheng , Chen Jinbo , Chen Zhiyong , Li Yang , Cui Yu , Chen Hequn 

TITLE=Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by lncRNA MALAT1 May Partially Contribute to Randall’s Plaque Formation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.596363

DOI=10.3389/fcell.2020.596363

ISSN=2296-634X

ABSTRACT=<sec><title>Background</title><p>The current belief is that Randall’s plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA <italic>MALAT1</italic> in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs).</p></sec><sec><title>Materials and Methods</title><p>Biomineralization and <italic>MALAT1</italic> expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in <italic>MALAT1</italic> were identified by 5′ and 3′ RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among <italic>MALAT1</italic>, <italic>Runx2</italic> and miRNAs.</p></sec><sec><title>Results</title><p>Upregulated expression of osteogenic markers and <italic>MALAT1</italic> was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of <italic>MALAT1</italic> promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of <italic>Runx2</italic> significantly suppressed the osteogenic phenotype. Further analysis showed that <italic>MALAT1</italic> functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs.</p></sec><sec><title>Conclusion</title><p>Ectopic calcification and <italic>MALAT1</italic> partially contributed to the formation of RP, in which <italic>MALAT1</italic> might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.</p></sec>