Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations

Abstract Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic respons...

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Autores principales:	Ariana Dela Cruz, Vinay Kartha, Andrew Tilston-Lunel, Rongjuan Mi, Taylor L. Reynolds, Michael Mingueneau, Stefano Monti, Janicke L. Jensen, Kathrine Skarstein, Xaralabos Varelas, Maria A. Kukuruzinska
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78b4ac9190c74b908615a330e8a4a60e
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spelling	oai:doaj.org-article:78b4ac9190c74b908615a330e8a4a60e2021-12-02T14:42:20ZGene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations10.1038/s41598-021-90569-w2045-2322https://doaj.org/article/78b4ac9190c74b908615a330e8a4a60e2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90569-whttps://doaj.org/toc/2045-2322Abstract Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.Ariana Dela CruzVinay KarthaAndrew Tilston-LunelRongjuan MiTaylor L. ReynoldsMichael MingueneauStefano MontiJanicke L. JensenKathrine SkarsteinXaralabos VarelasMaria A. KukuruzinskaNature 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 Ariana Dela Cruz Vinay Kartha Andrew Tilston-Lunel Rongjuan Mi Taylor L. Reynolds Michael Mingueneau Stefano Monti Janicke L. Jensen Kathrine Skarstein Xaralabos Varelas Maria A. Kukuruzinska Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
description	Abstract Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.
format	article
author	Ariana Dela Cruz Vinay Kartha Andrew Tilston-Lunel Rongjuan Mi Taylor L. Reynolds Michael Mingueneau Stefano Monti Janicke L. Jensen Kathrine Skarstein Xaralabos Varelas Maria A. Kukuruzinska
author_facet	Ariana Dela Cruz Vinay Kartha Andrew Tilston-Lunel Rongjuan Mi Taylor L. Reynolds Michael Mingueneau Stefano Monti Janicke L. Jensen Kathrine Skarstein Xaralabos Varelas Maria A. Kukuruzinska
author_sort	Ariana Dela Cruz
title	Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
title_short	Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
title_full	Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
title_fullStr	Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
title_full_unstemmed	Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
title_sort	gene expression alterations in salivary gland epithelia of sjögren’s syndrome patients are associated with clinical and histopathological manifestations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/78b4ac9190c74b908615a330e8a4a60e
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Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations

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