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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2021-06-01
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doaj-f7a8ead37e6f4c018d04212e92161ec42021-06-06T11:35:02ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111210.1038/s41598-021-91016-6Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitisMotoko Sasaki0Yasunori Sato1Yasuni Nakanuma2Department of Human Pathology, Kanazawa University Graduate School of Medical SciencesDepartment of Human Pathology, Kanazawa University Graduate School of Medical SciencesDepartment of Pathology, Fukui Saiseikai HospitalAbstract 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.https://doi.org/10.1038/s41598-021-91016-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Motoko Sasaki Yasunori Sato Yasuni Nakanuma |
spellingShingle |
Motoko Sasaki Yasunori Sato Yasuni Nakanuma Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-06-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-91016-6 |
work_keys_str_mv |
AT motokosasaki interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis AT yasunorisato interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis AT yasuninakanuma interferoninducedproteinwithtetratricopeptiderepeats3maybeakeyfactorinprimarybiliarycholangitis |
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