Objective: Systemic sclerosis (SSc) is an autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Cadherin-11 (CDH11) expression is increased in fibrotic skin and lung tissue. Targeting CDH11 may be an effective approach to treating fibrosis. We hypothesize that targeting CDH11 will decrease fibrosis in the tight skin-1 (Tsk-1) mouse model.
Methods: CDH11 expression was determined in the Tsk-1 mouse model using quantitative real time PCR and immunofluorescence (IF). Inhibitory anti- CDH11 monoclonal antibodies were tested in Tsk-1 mice for their ability to decrease hypodermal fibrosis.
Results: Expression of CDH11 was increased in fibrotic skin from Tsk-1 mice compared to pallid controls. IF staining demonstrated that CDH11 expression localized to fibroblasts within the hypodermis of fibrotic skin. Treatment with inhibitory anti-CDH11 monoclonal antibodies decreased hypodermal thickness and fibrotic mediators in Tsk-1 mice compared to control antibodies.
Conclusions: These data demonstrate an important role for CDH11 in the development of skin fibrosis in Tsk-1 mice. These data add to the growing evidence for the important role of CDH11 in tissue fibrosis and fibrotic disease such as systemic sclerosis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675431 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187109 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Objective: S100A4 is a DAMP protein. S100A4 is overexpressed in patients with systemic sclerosis (SSc), and levels correlate with organ involvement and disease activity. S100A4 mice are protected from fibrosis.
View Article and Find Full Text PDFIguratimod attenuated fibrosis in systemic sclerosis via targeting early growth response 1 expression.
Arthritis Res Ther
August 2023
Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China.
Article Synopsis
- EGR1 is a key factor involved in a disease called systemic sclerosis (SSc), which causes thickening of the skin.
- Iguratimod is a new drug that lowers the levels of EGR1, helping to improve conditions in skin cells affected by SSc.
- The study found that iguratimod reduces skin fibrosis and lessens important markers, hinting that lowering EGR1 could be a way to help treat this disease.
Estrogens Counteract the Profibrotic Effects of TGF-β and their Inhibition Exacerbates Experimental Dermal Fibrosis.
J Invest Dermatol
March 2020
Université Paris Descartes, Sorbonne Paris Cité, INSERM U1016 and CNRS UMR8104, Institut Cochin, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Service de Rhumatologie A, Hôpital Cochin, Paris, France.
Systemic sclerosis primarily affects women. This sex bias raises the question on the role female hormones could play in the development of fibrosis, which is largely unknown. Our aim was to evaluate the effects of estrogens in the development of experimental dermal fibrosis, in the mouse models of bleomycin-induced dermal fibrosis and tight skin (Tsk-1) mice, and on the activation of dermal fibroblasts by transforming growth factor-β (TGF-β).
View Article and Find Full Text PDFPoly(ADP-ribose) polymerase-1 regulates fibroblast activation in systemic sclerosis.
Ann Rheum Dis
May 2018
Department of Internal Medicine 3 for Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital of Erlangen, Erlangen, Germany.
Objectives: The enzyme poly(ADP-ribose) polymerase-1 (PARP-1) transfers negatively charged ADP-ribose units to target proteins. This modification can have pronounced regulatory effects on target proteins. Recent studies showed that PARP-1 can poly(ADP-ribosyl)ate (PARylate) Smad proteins.
View Article and Find Full Text PDFTargeting of cadherin-11 decreases skin fibrosis in the tight skin-1 mouse model.
PLoS One
November 2017
Section of Immunology, Allergy, and Rheumatology, Biology of Inflammation Center, Department of Medicine, Baylor College of Medicine, Houston, TX, United States of America.
Objective: Systemic sclerosis (SSc) is an autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Cadherin-11 (CDH11) expression is increased in fibrotic skin and lung tissue. Targeting CDH11 may be an effective approach to treating fibrosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!