title: miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis.
abstract: The objective of this study was to investigate the role of miR-148a-3p in lupus nephritis (LN) based on data from previous studies and a microRNA assay. We evaluated the miR-148a-3p expression level in LN renal tissues and blood serum to determine its clinicopathological significance and effect on glomerular cell proliferation. Then, we collected renal glomeruli from LN mice and determined the miR-148a-3p, proliferating cell nuclear antigen (PCNA), and PCNA/Thy1 expression. We performed functional analyses of miR-148a-3p in vitro and in vivo. We also investigated the target gene of miR-148a-3p in LN. The results showed that miR-148a-3p expression levels were significantly higher not only in glomeruli but also in the blood serum during LN and increased in the glomeruli of LN mice and that at the same time there was positive correlation between miR-148a-3p and PCNA expression of glomruli. Overexpression of miR-148a-3p accelerated cell proliferation and PCNA expression, while a miR-148a-3p inhibitor inhibited cell proliferation via the Akt/cyclin D1 pathway. Furthermore, miR-148a-3p overexpression reduced the phosphatase and tensin homology deleted on chromosome ten (PTEN) expression level, while miR-148a-3p silencing increased its expression in high-mobility group box 1 (HMGB1)-induced mouse mesangial cells (MMCs). Luciferase assays demonstrated that miR-148a-3p could directly bind to the PTEN 3'-UTR. PTEN overexpression inhibited MMC proliferation considerably, resembling the results observed during miR-148a-3p inhibition. Reducing miR-148a-3p expression upregulated PTEN in the glomeruli and improved renal function in LN mice. Thus miR-148a-3p may promote proliferation and contribute to LN progression by targeting PTEN.
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Liu
authors.initials: L
authors.lastname: Qingjuan
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Feng
authors.initials: F
authors.lastname: Xiaojuan
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Wu
authors.initials: W
authors.lastname: Chao
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Kang
authors.initials: K
authors.lastname: Pengpeng
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Li
authors.initials: L
authors.lastname: Hongbo
authors.affiliation: Department of Hand and Foot Surgery, Third Hospital of Shijiazhuang City, Shijiazhuang, China; and.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Sanbing
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China;
authors.forename: Hao
authors.initials: H
authors.lastname: Jun
authors.affiliation: Department of Pathology, Shijiazhuang people's medical college, Shijiazhuang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Min
authors.affiliation: Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China; susanliu2001@hotmail.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Shuxia
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D024243:HMGB1 Protein / Q000235:genetics; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics* / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D024243:HMGB1 Protein; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PTEN; cell proliferation; diagnosis; lupus nephritis; miR-148a-3p; therapy