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Association of endothelial to mesenchymal transition and cellular senescence with fibrosis in skin biopsies of systemic sclerosis patients: a cross-sectional study.
Chiu, Yu-Hsiang; Spierings, Julia; van Laar, Jacob M; de Vries-Bouwstra, Jeska K; van Dijk, Marijke; Goldschmeding, Roel.
Afiliación
  • Chiu YH; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; and Division of Rheumatology/Immunology/Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • Spierings J; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • van Laar JM; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • de Vries-Bouwstra JK; The Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
  • van Dijk M; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Goldschmeding R; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands. r.goldschmeding@umcutrecht.nl.
Clin Exp Rheumatol ; 41(8): 1612-1617, 2023 Aug.
Article en En | MEDLINE | ID: mdl-37382464
OBJECTIVES: Fibrosis is the dominant hallmark of systemic sclerosis (SSc). Several mechanisms have been proposed to drive the disease process, but how these relate to skin fibrosis is poorly understood. METHODS: We performed a cross-sectional study on archival skin biopsies from 18 SSc patients and four controls. Dermal fibrosis and inflammatory cell infiltration were scored in HE and Masson's Trichrome-stained sections. The presence of senescence was defined by P21 and/or P16 positivity in Ki-67 negative cells. Endothelial to mesenchymal transition (EndMT) was identified by co-localisation of CD31 and α-SMA in immunofluorescent double-stained sections, and by an enclosure of ERG positive endothelial cell nuclei by α-SMA stained cytoplasm in immunohistochemical double staining. RESULTS: The histological dermal fibrosis score of SSc skin biopsies was correlated with the modified Rodnan skin score (rho 0.55, p=0.042). Staining for markers of cellular senescence on fibroblasts was correlated with fibrosis score, inflammatory score, and CCN2 staining on fibroblasts. Moreover, EndMT was more abundant in skin from patients with SSc (p<0.01) but did not differ between groups with different fibrosis severity. The frequency of these EndMT features increased with the abundance of senescence markers and CCN2 on fibroblasts and dermal inflammation. CONCLUSIONS: EndMT and fibroblast senescence were more abundant in skin biopsies from SSc patients. This finding indicates that both senescence and EndMT are involved in the pathway leading to skin fibrosis and might be valuable biomarkers and/or possible targets for novel therapeutic interventions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica Tipo de estudio: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Exp Rheumatol Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Italia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica Tipo de estudio: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Exp Rheumatol Año: 2023 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Italia