Department of Biology and Genetics Institute, University of Florida, Gainesville, FL, United States of America.
PLoS One. 2023 May 8;18(5):e0285328. doi: 10.1371/journal.pone.0285328. eCollection 2023.
In epidermal tissues, extracellular matrices (ECMs) function as barriers between the organism and environment. Despite being at the interface with the environment, little is known about the role of animal barrier ECMs in sensing stress and communicating with cytoprotective gene pathways in neighboring cells. We and others have identified a putative damage sensor in the C. elegans cuticle that regulates osmotic, detoxification, and innate immune response genes. This pathway is associated with circumferential collagen bands called annular furrows; mutation or loss of furrow collagens causes constitutive activation of osmotic, detoxification, and innate immune response genes. Here, we performed a genome-wide RNAi screen for modulators of osmotic stress response gene gpdh-1 in a furrow collagen mutant strain. RNAi of six genes identified in this screen were tested under other conditions and for effects on other stress responses. The functions of these genes suggest negative feedback within osmolyte accumulation pathways and interactions with ATP homeostasis and protein synthesis. Loss of these gpdh-1 modulators had distinct effects on canonical detoxification and innate immune response genes.
在表皮组织中，细胞外基质（ECM）作为生物体与环境之间的屏障发挥作用。尽管处于与环境的界面处，但对于动物屏障 ECM 在感知应激和与相邻细胞中的细胞保护基因途径进行通信中的作用知之甚少。我们和其他人已经在秀丽隐杆线虫的表皮中鉴定出一种假定的损伤传感器，该传感器调节渗透、解毒和先天免疫反应基因。该途径与称为环状皱襞的环形胶原带相关；皱襞胶原的突变或缺失会导致渗透、解毒和先天免疫反应基因的组成性激活。在这里，我们在皱襞胶原突变株中进行了全基因组 RNAi 筛选，以寻找渗透胁迫反应基因 gpdh-1 的调节剂。对该筛选中鉴定出的六个基因的 RNAi 进行了其他条件下的测试，并检测了它们对其他应激反应的影响。这些基因的功能表明在渗透调节剂积累途径中存在负反馈，以及与 ATP 稳态和蛋白质合成的相互作用。这些 gpdh-1 调节剂的缺失对典型的解毒和先天免疫反应基因有明显的影响。
