Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM

被引:13
作者
Blokland, Kaj E. C. [1 ,2 ,3 ,4 ]
Habibie, Habibie [2 ,5 ,6 ]
Borghuis, Theo [1 ,2 ]
Teitsma, Greta J. [1 ,2 ]
Schuliga, Michael [3 ]
Melgert, Barbro N. [1 ,2 ,5 ]
Knight, Darryl A. [3 ,4 ,7 ]
Brandsma, Corry-Anke [1 ,2 ]
Pouwels, Simon D. [1 ,2 ,8 ]
Burgess, Janette K. [1 ,2 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 GZ Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD, NL-9713 GZ Groningen, Netherlands
[3] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia
[4] Natl Hlth & Med Res Council Ctr Res Excellence Pu, Sydney, NSW 2050, Australia
[5] Univ Groningen, Groningen Res Inst Pharm, Dept Mol Pharmacol, NL-9713 GZ Groningen, Netherlands
[6] Hasanuddin Univ, Fac Pharm, Makassar 90245, Indonesia
[7] Univ British Columbia, Providence Hlth Care Res Inst, Dept Anesthesiol Pharmacol & Therapeut, Vancouver, BC V6Z 1Y6, Canada
[8] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, NL-9713 GZ Groningen, Netherlands
关键词
extracellular matrix; senescence; idiopathic pulmonary fibrosis; proinflammatory; profibrotic; EXTRACELLULAR-MATRIX; PROTEINS; CELLS; IMAGE;
D O I
10.3390/cells10071628
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16(Ink4a) and p21(Waf1/Cip1). However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor beta 1 (TGF-beta 1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF.
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页数:18
相关论文
共 42 条
  • [11] Chronic WNT/β-catenin signaling induces cellular senescence in lung epithelial cells
    Lehmann, Mareike
    Hu, Qianjiang
    Hu, Yan
    Hafner, Kathrin
    Costa, Rita
    van den Berg, Anastasia
    Koenigshoff, Melanie
    [J]. CELLULAR SIGNALLING, 2020, 70
  • [12] The ECM path of senescence in aging: components and modifiers
    Levi, Naama
    Papismadov, Nurit
    Solomonov, Inna
    Sagi, Irit
    Krizhanovsky, Valery
    [J]. FEBS JOURNAL, 2020, 287 (13) : 2636 - 2646
  • [13] RETRACTED: Effects of Fibronectin 1 on Cell Proliferation, Senescence and Apoptosis of Human Glioma Cells Through the PI3K/AKT Signaling Pathway (Retracted Article)
    Liao, Yu -Xiang
    Zhang, Zhi-Ping
    Zhao, Jie
    Liu, Jing-Ping
    [J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 48 (03) : 1382 - 1396
  • [14] Cell senescence and fibrotic lung diseases
    Liu, Rui-Ming
    Liu, Gang
    [J]. EXPERIMENTAL GERONTOLOGY, 2020, 132
  • [15] Comparison of decellularization techniques for preparation of extracellular matrix scaffolds derived from three-dimensional cell culture
    Lu, Hongxu
    Hoshiba, Takashi
    Kawazoe, Naoki
    Chen, Guoping
    [J]. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2012, 100A (09) : 2507 - 2516
  • [16] Senescent Cells in IPF: Locked in Repair?
    Meiners, Silke
    Lehmann, Mareike
    [J]. FRONTIERS IN MEDICINE, 2020, 7
  • [17] Hallmarks of the ageing lung
    Meiners, Silke
    Eickelberg, Oliver
    Koenigshoff, Melanie
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2015, 45 (03) : 807 - 827
  • [18] The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis
    Murtha, Lucy A.
    Morten, Matthew
    Schuliga, Michael J.
    Mabotuwana, Nishani S.
    Hardy, Sean A.
    Waters, David W.
    Burgess, Janette K.
    Ngo, Doan T. M.
    Sverdlov, Aaron L.
    Knight, Darryl A.
    Boyle, Andrew J.
    [J]. AGING AND DISEASE, 2019, 10 (02): : 419 - 428
  • [19] Donor age-dependent acceleration of cellular aging by repeated ultraviolet A irradiation of human dermal fibroblasts derived from a single donor
    Naru, Eiji
    Ohta, Toshiro
    Inomata, Ken
    Hayashi, Akinobu
    Kaji, Kazuhiko
    [J]. HUMAN CELL, 2009, 22 (02) : 31 - 37
  • [20] Noordhoek Jacobien A, 2005, COPD, V2, P17