Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis

Abstract Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined comprehensive profiles of senescent...

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Autores principales:	Motoko Sasaki, Yasunori Sato, Yasuni Nakanuma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7a8ead37e6f4c018d04212e92161ec4
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spelling	oai:doaj.org-article:f7a8ead37e6f4c018d04212e92161ec42021-12-02T15:56:49ZInterferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis10.1038/s41598-021-91016-62045-2322https://doaj.org/article/f7a8ead37e6f4c018d04212e92161ec42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91016-6https://doaj.org/toc/2045-2322Abstract Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined comprehensive profiles of senescent BECs and its contribution to the pathogenesis of PBC taking advantage of microarray analysis. cDNA microarray analysis revealed that 1841 genes including CCL2, IFIT3, CPQ were commonly up-regulated in senescent BECs cultured in serum depleted media or media with glycochenodeoxycholic acid. Knockdown of IFIT3 significantly suppressed cellular senescence (p < 0.01) and significantly increased apoptosis (p < 0.01) in BECs treated with serum depletion or glycochenodeoxycholic acid. Significantly increased expression of IFIT3 was seen in senescent BECs in small bile ducts showing cholangitis and in ductular reactions in PBC, compared to control livers (p < 0.01). An inadequate response to UDCA was inversely correlated to the increased expression of IFIT3 in small bile duct in PBC (p < 0.05). In conclusion, the expression of various genes related to immunity and inflammation including SASPs were increased in senescent BECs. Upregulated IFIT3 in senescent BECs may be associated with the pathogenesis of PBC and may be a possible therapeutic target in PBC.Motoko SasakiYasunori SatoYasuni NakanumaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Motoko Sasaki Yasunori Sato Yasuni Nakanuma Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
description	Abstract Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined comprehensive profiles of senescent BECs and its contribution to the pathogenesis of PBC taking advantage of microarray analysis. cDNA microarray analysis revealed that 1841 genes including CCL2, IFIT3, CPQ were commonly up-regulated in senescent BECs cultured in serum depleted media or media with glycochenodeoxycholic acid. Knockdown of IFIT3 significantly suppressed cellular senescence (p < 0.01) and significantly increased apoptosis (p < 0.01) in BECs treated with serum depletion or glycochenodeoxycholic acid. Significantly increased expression of IFIT3 was seen in senescent BECs in small bile ducts showing cholangitis and in ductular reactions in PBC, compared to control livers (p < 0.01). An inadequate response to UDCA was inversely correlated to the increased expression of IFIT3 in small bile duct in PBC (p < 0.05). In conclusion, the expression of various genes related to immunity and inflammation including SASPs were increased in senescent BECs. Upregulated IFIT3 in senescent BECs may be associated with the pathogenesis of PBC and may be a possible therapeutic target in PBC.
format	article
author	Motoko Sasaki Yasunori Sato Yasuni Nakanuma
author_facet	Motoko Sasaki Yasunori Sato Yasuni Nakanuma
author_sort	Motoko Sasaki
title	Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
title_short	Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
title_full	Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
title_fullStr	Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
title_full_unstemmed	Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
title_sort	interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f7a8ead37e6f4c018d04212e92161ec4
work_keys_str_mv	AT motokosasaki interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis AT yasunorisato interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis AT yasuninakanuma interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis
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Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis

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