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ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy

BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives...

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Autores principales: Liu, Youxia, Zheng, Jie, Zhao, Na, Jia, Junya, Yan, Tiekun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589307/
https://www.ncbi.nlm.nih.gov/pubmed/31275443
http://dx.doi.org/10.1155/2019/2407067
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author Liu, Youxia
Zheng, Jie
Zhao, Na
Jia, Junya
Yan, Tiekun
author_facet Liu, Youxia
Zheng, Jie
Zhao, Na
Jia, Junya
Yan, Tiekun
author_sort Liu, Youxia
collection PubMed
description BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives secretory-specific Ig mRNA production. METHODS: We enrolled 21 patients with IgAN, 18 healthy controls, and 20 patients with non-IgAN glomerulonephritis. The differential expression of ELL2 was compared using publically available data from Gene Expression Omnibus (GEO) datasets. The relationship between ELL2 expressions and galactose-deficient IgA1 (Gd-IgA1) levels in serum were also studied. At last, the results were validated by shELL2 treatment experiment. RESULTS: We found that the number of CD19+ B cells was increased in IgAN patients compared to healthy controls. The expression level of ELL2 in patients with IgAN was significantly lower than that of healthy control and disease control. Consistent with present results, the lower ELL2 expression in IgAN patients was observed in microarray expression profiles from GEO datasets. Pearson correlation analysis showed that ELL2 expression negatively correlated with Gd-IgA1 levels. Furthermore, in an in vitro experiment, we found that loss of ELL2 function in human B lymphoma DAKIKI cells, an IgA1-producing cell line, increased the levels of Gd-IgA1, which confirmed that ELL2 modulated the levels of Gd-IgA1. CONCLUSION: Our findings implied that decreased ELL2 expression was negatively correlated with the numbers of B cells and aberrant glycosylation of IgA1 in IgAN.
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spelling pubmed-65893072019-07-04 ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy Liu, Youxia Zheng, Jie Zhao, Na Jia, Junya Yan, Tiekun Dis Markers Research Article BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives secretory-specific Ig mRNA production. METHODS: We enrolled 21 patients with IgAN, 18 healthy controls, and 20 patients with non-IgAN glomerulonephritis. The differential expression of ELL2 was compared using publically available data from Gene Expression Omnibus (GEO) datasets. The relationship between ELL2 expressions and galactose-deficient IgA1 (Gd-IgA1) levels in serum were also studied. At last, the results were validated by shELL2 treatment experiment. RESULTS: We found that the number of CD19+ B cells was increased in IgAN patients compared to healthy controls. The expression level of ELL2 in patients with IgAN was significantly lower than that of healthy control and disease control. Consistent with present results, the lower ELL2 expression in IgAN patients was observed in microarray expression profiles from GEO datasets. Pearson correlation analysis showed that ELL2 expression negatively correlated with Gd-IgA1 levels. Furthermore, in an in vitro experiment, we found that loss of ELL2 function in human B lymphoma DAKIKI cells, an IgA1-producing cell line, increased the levels of Gd-IgA1, which confirmed that ELL2 modulated the levels of Gd-IgA1. CONCLUSION: Our findings implied that decreased ELL2 expression was negatively correlated with the numbers of B cells and aberrant glycosylation of IgA1 in IgAN. Hindawi 2019-06-04 /pmc/articles/PMC6589307/ /pubmed/31275443 http://dx.doi.org/10.1155/2019/2407067 Text en Copyright © 2019 Youxia Liu et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Youxia
Zheng, Jie
Zhao, Na
Jia, Junya
Yan, Tiekun
ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title_full ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title_fullStr ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title_full_unstemmed ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title_short ELL2 Is Downregulated and Associated with Galactose-Deficient IgA1 in IgA Nephropathy
title_sort ell2 is downregulated and associated with galactose-deficient iga1 in iga nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589307/
https://www.ncbi.nlm.nih.gov/pubmed/31275443
http://dx.doi.org/10.1155/2019/2407067
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