Abstract:
Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in such forces can influence structural organization, homeostasis, and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells. In this study, we investigate the potential role of adenomatous polyposis coli (APC) in modulating tissue tension. Our findings reveal that expression of an APC truncation mutant elevates epithelial tension via the RhoA/ROCK pathway. This elevation induces morphological alterations and hampers apoptotic cell extrusion in cultured epithelial cells and organoids, both of which could be mitigated by pharmacologically restoring the tissue tension. This raises the possibility that APC mutations may exert pathogenetic effects by altering tissue mechanics.
摘要:
组织张力包括施加在动物体内实体组织上的机械力,源自各种来源,如细胞收缩性,与邻近细胞和细胞外基质的相互作用。新出现的证据表明,这种力量的不平衡会影响结构组织,稳态,并可能导致疾病。例如,升高的组织张力可以阻碍根尖细胞的挤压,导致凋亡或转化细胞的保留。在这项研究中,我们研究了腺瘤性结肠息肉病(APC)在调节组织张力中的潜在作用。我们的发现揭示了APC截短突变体的表达通过RhoA/ROCK途径升高上皮张力。这种升高诱导培养的上皮细胞和类器官中的形态学改变并阻碍凋亡细胞挤出,这两者都可以通过药理学恢复组织张力来缓解。这增加了APC突变可能通过改变组织力学而发挥致病作用的可能性。