Reacquisition of a spindle cell shape does not lead to the restoration of a youthful state in senescent human skin fibro
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RESEARCH ARTICLE
Reacquisition of a spindle cell shape does not lead to the restoration of a youthful state in senescent human skin fibroblasts Adamantia Papadopoulou . Anastasia Kanioura . Panagiota S. Petrou . Panagiotis Argitis . Sotirios E. Kakabakos . Dimitris Kletsas
Received: 16 March 2020 / Accepted: 5 June 2020 Ó Springer Nature B.V. 2020
Abstract Senescent fibroblasts are characterized by their inability to proliferate and by a pro-inflammatory and catabolic secretory phenotype, which contributes to age-related pathologies. Furthermore, senescent fibroblasts when cultured under classical conditions in vitro are also characterized by striking morphological changes, i.e. they lose the youthful spindle-like appearance and become enlarged and flattened, while their nuclei from elliptical become oversized and highly lobulated. Knowing the strong relation between cell shape and function, we cultured human senescent fibroblasts on photolithographed Si/poly(vinyl alcohol) (PVA) micro-patterned surfaces in order to restore the classical spindle-like geometry and subsequently to investigate whether the changes in A. Papadopoulou D. Kletsas (&) Laboratory of Cell Proliferation & Ageing, Institute of Biosciences & Applications, National Centre for Scientific Research ‘‘Demokritos’’, P. Grigoriou Str, Ag. Paraskevi, 15341 Athens, Greece e-mail: [email protected] A. Kanioura P. S. Petrou S. E. Kakabakos Immunoassays/Immunosensors Laboratory, Institute of Nuclear and Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research ‘‘Demokritos’’, P. Grigoriou Str, Ag. Paraskevi, 15341 Athens, Greece P. Argitis Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research ‘‘Demokritos’’, P. Grigoriou Str, Ag. Paraskevi, 15341 Athens, Greece
senescent cells’ morphology are the cause of their functional alterations. Interestingly, under these conditions senescent cells’ nuclei do not revert to the classical elliptical phenotype. Furthermore, enforced spindle-shaped senescent cells retained their deteriorated proliferative ability, and maintained the increased gene expression of the cell cycle inhibitors p16Ink4a and p21Waf1. In addition, Si/PVA-patternedgrown senescent fibroblasts preserved their senescence-associated phenotype, as evidenced by the overexpression of inflammatory and catabolic genes such as IL6, IL8, ICAM1 and MMP1 and MMP9 respectively, which was further manifested by an intense downregulation of fibroblasts’ most abundant extracellular matrix component Col1A, compared to their young counterparts. These data indicate that the restoration of the spindle-like shape in senescent human fibroblasts is not able to directly alter major functional traits and restore the youthful phenotype. Keywords Senescence Fibroblast Cell shape SASP Lithography
Introduction As opposed to classic cell culture conditions, cells within tissues and organs, are confined into a highly structured microenvironme
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