Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland.
Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA.
Sci Adv. 2023 Sep;9(35):eadh9219. doi: 10.1126/sciadv.adh9219. Epub 2023 Aug 30.
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.
高渗应激发生在多种疾病中，但它的长期影响在很大程度上尚不清楚。我们使用山梨醇处理的人成纤维细胞进行 3D 培养，以研究皮肤中高渗应激的后果。山梨醇调节了许多有助于细胞应对应激条件的基因。调节最明显的基因编码丝氨酸蛋白酶 35（PRSS35）。其受高渗应激的调节依赖于激酶 p38 和 JNK 以及转录因子 NFAT5 和 ATF2。我们鉴定了不同的胶原和胶原相关蛋白作为潜在的 PRSS35 结合伴侣。这在功能上很重要，因为 PRSS35 影响细胞外基质蛋白质组，从而限制细胞增殖。这些发现的体内相关性反映在人类皮肤伤口中 PRSS35 及其结合伴侣的共表达上，高渗应激是由于过度失水而发生的。这些结果表明 PRSS35 是高渗应激条件下基质组的关键调节剂。
