Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Department of Immunology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
Int J Mol Sci. 2024 Mar 7;25(6):3084. doi: 10.3390/ijms25063084.
The retina is a central nervous tissue essential to visual perception and highly susceptible to environmental damage. Lower vertebrate retinas activate intrinsic regeneration mechanisms in response to retinal injury regulated by a specialized population of progenitor cells. The mammalian retina does not have populations of progenitor/stem cells available to activate regeneration, but contains a subpopulation of differentiated cells that can be reprogrammed into retinal stem cells, the ciliary epithelium (CE) cells. Despite the regenerative potential, stem cells derived from CE exhibit limited reprogramming capacity probably associated with the expression of intrinsic regulatory mechanisms. Platelet-activating factor (PAF) is a lipid mediator widely expressed in many cells and plays an important role in stem cell proliferation and differentiation. During mammalian development, PAF receptor signaling showed important effects on retinal progenitors' cell cycle regulation and neuronal differentiation that need to be further investigated. In this study, our findings suggested a dynamic role for PAF receptor signaling in CE cells, impacting stem cell characteristics and neurosphere formation. We showed that PAF receptors and PAF-related enzymes are downregulated in retinal progenitor/stem cells derived from PE cells. Blocking PAFR activity using antagonists increased the expression of specific progenitor markers, revealing potential implications for retinal tissue development and maintenance.
视网膜是一种对视觉感知至关重要的中枢神经系统组织,极易受到环境损害。较低等脊椎动物的视网膜会在视网膜损伤时激活内在的再生机制,这一过程受到特定祖细胞群体的调控。哺乳动物的视网膜没有可供激活再生的祖细胞/干细胞群体,但含有可被重新编程为视网膜干细胞的分化细胞亚群,即睫状上皮(CE)细胞。尽管具有再生潜力,但源自 CE 的干细胞的重编程能力有限,这可能与内在调控机制的表达有关。血小板激活因子(PAF)是一种广泛存在于许多细胞中的脂质介质,在干细胞增殖和分化中发挥着重要作用。在哺乳动物发育过程中,PAF 受体信号对视网膜祖细胞的细胞周期调控和神经元分化有重要影响,需要进一步研究。在这项研究中,我们的发现表明 PAF 受体信号在 CE 细胞中发挥动态作用,影响干细胞特性和神经球形成。我们表明,源自 PE 细胞的视网膜祖细胞/干细胞中 PAF 受体和 PAF 相关酶的表达下调。使用拮抗剂阻断 PAFR 活性会增加特定祖细胞标志物的表达,这表明其对视网膜组织发育和维持具有潜在意义。
Stem Cell Res Ther. 2021-10-30
Mol Vis. 2007-6-29
BMC Dev Biol. 2006-7-26
Invest Ophthalmol Vis Sci. 2014-4-21
Mol Neurobiol. 2022-7
Nucleic Acids Res. 2022-7-5
Front Endocrinol (Lausanne). 2021
Stem Cell Res Ther. 2021-1-25
Prostaglandins Other Lipid Mediat. 2021-4
Am J Transl Res. 2020-11-15