AI Article Synopsis
- Dermal fibrosis, a key characteristic of systemic sclerosis (SSc), currently lacks effective treatment, partly due to an incomplete understanding of white adipose tissue's role in skin fibrosis.
- Researchers found that SIX1, a gene associated with fibrosis, is elevated in SSc skin samples and correlates with other adipose-related genes.
- Deleting the SIX1 gene in both general and adipocyte-specific models reduced fibrosis-related gene expression and prevented fat cell shrinkage, suggesting that targeting SIX1 could be a promising therapeutic approach for SSc-related skin fibrosis.
Article Abstract
Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited treatment strategies. This is in part due to our fragmented understanding of how dermal white adipose tissue (DWAT) contributes to skin fibrosis. We identified elevated sine oculis homeobox homolog 1 (SIX1) expression in SSc skin samples from the GENISOS and PRESS cohorts, the expression of which correlated with adipose-associated genes and molecular pathways. SIX1 localization studies identified increased signals in the DWAT area in SSc and in experimental models of skin fibrosis. Global and adipocyte specific Six1 deletion abrogated end-stage fibrotic gene expression and dermal adipocyte shrinkage induced by SQ bleomycin treatment. Further studies revealed a link between elevated SIX1 and increased expression of SERPINE1 and its protein PAI-1 which are known pro-fibrotic mediators. However, SIX1 deletion did not appear to affect cellular trans differentiation. Taken together these results point at SIX1 as a potential target for dermal fibrosis in SSc.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142148 | PMC |
| http://dx.doi.org/10.1101/2024.05.22.595271 | DOI Listing |
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