Date: Sunday, October 21, 2018
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Results: Unbiased transcriptome analysis of SSc skin and lung biopsies revealed significantly decreased A20 levels and robust anti-correlation with fibrotic TGF-ß signaling (r=-0.84, p<0.005). Lesional skin myofibroblasts in SSc showed a notable absence of A20 expression. In vitro, A20 expression was markedly reduced in fibroblasts treated with TGF-ß. Moreover, TGF-ß abrogated the stimulation of A20 elicited by TLR4. Remarkably, ectopic A20 in skin and lung fibroblasts abrogated profibrotic responses and disrupted Smad
We uncover a novel role for the SSc risk gene A20 as a fundamental checkpoint in modulating fibroblast activity and differentiation. Reduced A20 renders fibroblasts and transgenic mice susceptible to fibrosis. These observations suggest that reduced A20 in SSc patients carrying TNFAIP3 risk variants may underlie unchecked fibroblast activation and contribute to the pathogenesis of multiple organ fibrosis.
To cite this abstract in AMA style:Bhattacharyya S, Wang W, M. Jeong B, Abdala-Valencia H, Marangoni RG, Berdnikovs Ph.D. S, Varga J. Hypomorphic A20 Expression Modulates Fibrosis Susceptibility: Implications for Systemic Sclerosis? [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/hypomorphic-a20-expression-modulates-fibrosis-susceptibility-implications-for-systemic-sclerosis/. Accessed January 24, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hypomorphic-a20-expression-modulates-fibrosis-susceptibility-implications-for-systemic-sclerosis/