Klein Charlotte, Ramminger Imke, Bai Shuoqiu, Steinberg Thorsten, Tomakidi Pascal
Division of Oral Biotechnology, Center for Dental Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany.
Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
Cells. 2024 Nov 26;13(23):1960. doi: 10.3390/cells13231960.
Although cytoplasmic intermediate filaments (cIFs) are essential for cell physiology, the molecular and cell functional consequences of cIF disturbances are poorly understood. Identifying defaults in cell function-controlled tissue homeostasis and understanding the interrelationship between specific cIFs and distinct cell functions remain key challenges. Using an RNAi-based mechanistic approach, we connected the impairment of cell-inherent cIFs with molecular and cell functional consequences, such as proliferation and differentiation. To investigate cIF disruption consequences in the oral epithelium, different cell transformation stages, originating from alcohol-treated oral gingival keratinocytes, were used. We found that impairment of keratin (KRT) KRT5, KRT14 and vimentin (VIM) affects proliferation and differentiation, and modulates the chromatin status. Furthermore, cIF impairment reduces the expression of nuclear integrity participant lamin B1 and the terminal keratinocyte differentiation marker involucrin (IVL). Conversely, impairment of IVL reduces cIF expression levels, functionally suggesting a regulatory interaction between cIFs and IVL. The findings demonstrate that the impairment of cIFs leads to imbalances in proliferation and differentiation, both of which are essential for tissue homeostasis. Thus, targeted impairment of cIFs appears promising to investigate the functional role of cIFs on cell-dependent tissue physiology at the molecular level and identifies putative interactions of cIFs with epithelial differentiation.
尽管细胞质中间丝（cIFs）对细胞生理学至关重要，但对cIFs紊乱的分子和细胞功能后果却知之甚少。识别细胞功能控制的组织稳态中的缺陷以及理解特定cIFs与不同细胞功能之间的相互关系仍然是关键挑战。我们采用基于RNA干扰的机制方法，将细胞固有cIFs的损伤与分子和细胞功能后果（如增殖和分化）联系起来。为了研究口腔上皮中cIFs破坏的后果，我们使用了源自酒精处理的口腔牙龈角质形成细胞的不同细胞转化阶段。我们发现角蛋白（KRT）KRT5、KRT14和波形蛋白（VIM）的损伤会影响增殖和分化，并调节染色质状态。此外，cIFs损伤会降低核完整性相关蛋白核纤层蛋白B1和终末角质形成细胞分化标志物内披蛋白（IVL）的表达。相反，IVL的损伤会降低cIFs的表达水平，从功能上表明cIFs与IVL之间存在调节相互作用。这些发现表明，cIFs的损伤会导致增殖和分化失衡，而这两者对于组织稳态都至关重要。因此，有针对性地损伤cIFs似乎有望在分子水平上研究cIFs对细胞依赖性组织生理学的功能作用，并确定cIFs与上皮分化之间的假定相互作用。
