Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis

Autor: Anne Sofie Siebuhr, Michael J. Davies, Sandie Bondesen, Clare L. Hawkins, Morten A. Karsdal, Anne-Christine Bay-Jensen, Pernille Juhl
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Calcium Phosphates
0301 basic medicine
Indoles
LIVER
INTERLEUKIN-6
Receptor
Transforming Growth Factor-beta Type I
lcsh:Medicine
ACTIVATION
Extracellular matrix
chemistry.chemical_compound
Rheumatic diseases
0302 clinical medicine
Transforming Growth Factor beta
Fibrosis
VITRO
lcsh:Science
Skin
Platelet-Derived Growth Factor
Multidisciplinary
biology
Chemistry
Dermis
Extracellular Matrix
Nintedanib
Collagen
Platelet-derived growth factor receptor
Type I collagen
Cell biology
I COLLAGEN
Article
Transforming Growth Factor beta1
Dermal fibroblast
03 medical and health sciences
medicine
Humans
030203 arthritis & rheumatology
Interleukin-6
GROWTH-FACTOR-BETA
SYSTEMIC-SCLEROSIS
lcsh:R
Fibroblasts
medicine.disease
Molecular biology
Actins
Fibronectins
Fibronectin
030104 developmental biology
biology.protein
lcsh:Q
Transforming growth factor
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
Juhl, P, Bondesen, S, Hawkins, C L, Karsdal, M A, Bay-Jensen, A-C, Davies, M J & Siebuhr, A S 2020, ' Dermal fibroblasts have different extracellular matrix profiles induced by TGF-beta, PDGF and IL-6 in a model for skin fibrosis ', Scientific Reports, vol. 10, no. 1, 17300 . https://doi.org/10.1038/s41598-020-74179-6
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-020-74179-6
Popis: Different stimulants might induce different extracellular matrix profiles. It is essential to gain an understanding and quantification of these changes to allow for focused anti-fibrotic drug development. This study investigated the expression of extracellular matrix by dermal fibroblast mimicking fibrotic skin diseases as SSc using clinically validated biomarkers. Primary healthy human dermal fibroblasts were grown in media containing FICOLL. The cells were stimulated with PDGF-AB, TGF-β1, or IL-6. Anti-fibrotic compounds (iALK-5, Nintedanib) were added together with growth factors. Biomarkers of collagen formation and degradation together with fibronectin were evaluated by ELISAs in the collected supernatant. Immunohistochemical staining was performed to visualize fibroblasts and proteins, while selected gene expression levels were examined through qPCR. TGF-β and PDGF, and to a lesser extent IL-6, increased the metabolic activity of the fibroblasts. TGF-β primarily increased type I collagen and fibronectin protein and gene expression together with αSMA. PDGF stimulation resulted in increased type III and VI collagen formation and gene expression. IL-6 decreased fibronectin levels. iALK5 could inhibit TGF-β induced fibrosis while nintedanib could halt fibrosis induced by TGF-β or PDGF. Tocilizumab could not inhibit fibrosis induced in this model. The extent and nature of fibrosis are dependent on the stimulant. The model has potential as a pre-clinical model as the fibroblasts fibrotic phenotype could be reversed by an ALK5 inhibitor and Nintedanib.
Databáze: OpenAIRE
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