Serine protease 35 regulates the fibroblast matrisome in response to hyperosmotic stress
Abstract
Hyperosmotic stress occurs in several diseases, but its long-term effects are largely unknown. We used sorbitol-treated human fibroblasts in 3D culture to study the consequences of hyperosmotic stress in the skin. Sorbitol regulated many genes, which help cells cope with the stress condition. The most robustly regulated gene encodes serine protease 35 (PRSS35). Its regulation by hyperosmotic stress was dependent on the kinases p38 and JNK and the transcription factors NFAT5 and ATF2. We identified different collagens and collagen-associated proteins as putative PRSS35 binding partners. This is functionally important because PRSS35 affected the extracellular matrix proteome, which limited cell proliferation. The in vivo relevance of these findings is reflected by the coexpression of PRSS35 and its binding partners in human skin wounds, where hyperosmotic stress occurs as a consequence of excessive water loss. These results identify PRSS35 as a key regulator of the matrisome under hyperosmotic stress conditions. Show more
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https://doi.org/10.3929/ethz-b-000630227Publication status
publishedExternal links
Journal / series
Science AdvancesVolume
Pages / Article No.
Publisher
AAASOrganisational unit
09472 - Tibbitt, Mark / Tibbitt, Mark
03520 - Werner, Sabine / Werner, Sabine
03605 - Mazza, Edoardo / Mazza, Edoardo
Funding
189364 - Role of cytokines and environmental cues in inflammatory skin disease (SNF)
212212 - Control of skin inflammation by fibroblast growth factor signaling in keratinocytes (SNF)
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