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

Sasaki, Motoko; Sato, Yasunori; Nakanuma, Yasuni

doi:10.1038/s41598-021-91016-6

Cited by 11 publications

(7 citation statements)

References 42 publications

(84 reference statements)

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“…Of relevance, CCL2 and fractalkine expression was increased in inflamed bile ducts in human PBC samples (Sasaki et al, 2010a). Moreover, senescent small ducts in PBC also express genes associated with inflammation and immune response (Sasaki et al, 2021). This work further highlights that biliary senescence induces a pro-inflammatory secretome within damaged cholangiocytes, which promotes inflammation and the recruitment of various inflammatory cells.…”

Section: Primary Biliary Cholangitismentioning

confidence: 53%

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Meadows

Baiocchi

Kundu

et al. 2021

Front. Mol. Biosci.

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Cellular senescence is a pathophysiological phenomenon in which proliferative cells enter cell cycle arrest following DNA damage and other stress signals. Natural, permanent DNA damage can occur after repetitive cell division; however, acute stress or other injuries can push cells into premature senescence and eventually a senescence-associated secretory phenotype (SASP). In recent years, there has been increased evidence for the role of premature senescence in disease progression including diabetes, cardiac diseases, and end-stage liver diseases including cholestasis. Liver size and function change with aging, and presumably with increasing cellular senescence, so it is important to understand the mechanisms by which cellular senescence affects the functional nature of the liver in health and disease. As well, cells in a SASP state secrete a multitude of inflammatory and pro-fibrogenic factors that modulate the microenvironment. Cellular SASP and the associated, secreted factors have been implicated in the progression of liver diseases, such as cholestatic injury that target the biliary epithelial cells (i.e., cholangiocytes) lining the bile ducts. Indeed, cholangiocyte senescence/SASP is proposed to be a driver of disease phenotypes in a variety of liver injuries. Within this review, we will discuss the impact of cholangiocyte senescence and SASP in the pathogenesis of cholestatic disorders.

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Section: Primary Biliary Cholangitismentioning

confidence: 53%

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Meadows

Baiocchi

Kundu

et al. 2021

Front. Mol. Biosci.

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“…36 The upregulation of IFIT3 suppressed apoptosis of biliary epithelial cells and may be associated with the pathogenesis of primary biliary cholangitis. 37 Moreover, IFIT3 also plays a vital role in the inflammatory processes of noninflammatory diseases. The knockdown of IFIT3 could significantly suppress the release of inflammatory cytokines in hepatic ischemia-reperfusion injury via the inhibition of STAT1 and STAT2 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…IFIT3 could stimulate the activation of cGAS/STING signaling pathway, which accounted for the pathogenesis of systemic lupus erythematosus 36 . The upregulation of IFIT3 suppressed apoptosis of biliary epithelial cells and may be associated with the pathogenesis of primary biliary cholangitis 37 . Moreover, IFIT3 also plays a vital role in the inflammatory processes of noninflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Integrative bioinformatic analysis identified IFIT3 as a novel regulatory factor in psoriasis

Zhou

Wang

2022

J of Cellular Biochemistry

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Psoriasis is an autoimmune skin disease with poor prognosis. Currently, there is no cure for psoriasis and the pathogenic mechanism of psoriasis remains unclear. Our study aims to explore key regulators underlying psoriasis and potential targets for psoriasis treatment. RNA-seq data of psoriasis and normal tissues were extracted from Gene Expression Omnibus database to screen differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) was conducted to identify key gene modules correlated with psoriasis. Enrichment analysis was used to characterize identified genes. The expression of identified genes was verified in a data set with various types of psoriasis lesion tissues and six psoriasis and healthy control tissues by quantitative polymerase chain reaction and immunohistochemistry assays. And the biological functions of IFIT3 in keratinocytes were determined by colony formation assays, Cell Counting Kit-8, and enzyme-linked immunosorbent assays. A total of 594 overlapped genes (370 upregulated and 224 downregulated) were selected as DEGs between psoriasis and normal tissues in three independent data sets. These genes were enriched in interferon-related pathway and cytokine-related pathway. Weighted correlation network analysis identified several gene modules that were associated with psoriasis. Overlapped genes between gene modules and DEGs were associated with interferon-related pathway and T cell activities. Among these genes, OAS1, USP18, and IFIT3 had higher expression levels in psoriasis vulgaris (PV) and nonpustular palmoplantar psoriasis (NPPP) tissues but not Palmoplantar Pustular Psoriasis (PPPP).Meanwhile, these results were confirmed in our independent psoriasis tissue cohort. And results of in vitro experiments showed that inhibition of IFIT3 significantly impaired the proliferation capacity and CXCL1, CCL20, IL-1β, and IL-6 secretion of keratinocytes. Our study identified key genes and pathways underlying the pathogenesis of psoriasis through the conduct of integrated analysis. OAS1, USP18, and IFIT3 could be potential targets for the treatment of psoriasis.IFIT3 can promote the proliferation and immune activation of keratinocytes and facilitates the development of psoriasis.

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“…Sasaki and Nakanuma [31–33] previously reported that PBC patients exhibit increased senescent cholangiocytes; they also showed that, in vitro , the hydrophobic bile acid, GCDC promoted senescence likely via endoplasmic reticulum stress and dysregulated autophagy in cultured cholangiocytes [22]. More recently, Sasaki et al [34 ▪▪ ] performed a cDNA microarray analysis on cholangiocytes induced to senescence by serum depletion or persistent treatment with GCDC. The findings revealed increased expression of numerous chemokines and cytokines.…”

Section: Targetable Phenotypes Of Senescent Cholangiocytesmentioning

confidence: 99%

Cellular senescence in the cholangiopathies

Bogert

O’Hara

LaRusso

2021

Current Opinion in Gastroenterology

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Purpose of reviewCellular senescence (i.e. permanent withdrawal from the cell cycle) is increasingly recognized as a pathologic feature in a variety of inflammatory liver diseases, including primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and additional cholangiopathies. Herein, we provide an update on the interplay between cholangiocytes, cellular senescence and the cholangiopathies. Recent findingsThe themes covered by this review include novel models for studying the role of senescent cholangiocytes and the cholangiopathies, identification and modulation of key pathways or molecules regulating cholangiocyte senescence, and discovery of druggable targets to advance therapeutic options for the cholangiopathies. Most recent studies focused on PSC; however, the concepts and findings may be applied to additional cholangiopathies. SummaryCholangiopathies present unique and divergent clinicopathological features, causes and genetic backgrounds, but share several common disease processes. Cholangiocyte senescence in the cholestatic cholangiopathies, primarily PSC and PBC, is regarded as a key pathogenetic process. Importantly, senescent cholangiocytes exhibit phenotypic features including the senescence-associated secretory phenotype (SASP) and resistance to apoptosis that provide new directions for basic research and new prognostic and therapeutic approaches for clinical practice.

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

Cited by 11 publications

References 42 publications

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Biliary Epithelial Senescence in Liver Disease: There Will Be SASP

Integrative bioinformatic analysis identified IFIT3 as a novel regulatory factor in psoriasis

Cellular senescence in the cholangiopathies

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