scholarly journals Protease activated receptor-1 regulates macrophage-mediated cellular senescence: a risk for idiopathic pulmonary fibrosis

Oncotarget ◽  
2015 ◽  
Vol 6 (34) ◽  
pp. 35304-35314 ◽  
Author(s):  
Cong Lin ◽  
Farhad Rezaee ◽  
Maaike Waasdorp ◽  
Kun Shi ◽  
Tom van der Poll ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Protease Activated Receptor 1

scholarly journals Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Norihito Omote ◽  
Maor Sauler
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Disease ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Cellular Stress ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Non Coding Rnas

Cellular senescence is a cell fate implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Cellular senescence occurs in response to cellular stressors such as oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction. Whether these stresses induce cellular senescence or an alternative cell fate depends on the type and magnitude of cellular stress, but also on intrinsic factors regulating the cellular stress response. Non-coding RNAs, including both microRNAs and long non-coding RNAs, are key regulators of cellular stress responses and susceptibility to cellular senescence. In this review, we will discuss cellular mechanisms that contribute to senescence in IPF and COPD and highlight recent advances in our understanding of how these processes are influenced by non-coding RNAs. We will also discuss the potential therapeutic role for targeting non-coding RNAs to treat these chronic lung diseases.

scholarly journals What have we learned from basic science studies on idiopathic pulmonary fibrosis?

2019 ◽  
Vol 28 (153) ◽  
pp. 190029 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Seidai Sato ◽  
Chandak Upagupta ◽  
Martin Kolb
Keyword(s):  
Extracellular Matrix ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Basic Science ◽  
Science Studies ◽  
Cell Types ◽  
Age Related ◽  
Tremendous Progress

Idiopathic pulmonary fibrosis is a fatal age-related lung disease characterised by progressive and irreversible scarring of the lung. Although the details are not fully understood, there has been tremendous progress in understanding the pathogenesis of idiopathic pulmonary fibrosis, which has led to the identification of many new potential therapeutic targets. In this review we discuss several of these advances with a focus on genetic susceptibility and cellular senescence primarily affecting epithelial cells, activation of profibrotic pathways, disease-enhancing fibrogenic cell types and the role of the remodelled extracellular matrix.

scholarly journals miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0158367 ◽  
Author(s):  
Supparerk Disayabutr ◽  
Eun Kyung Kim ◽  
Seung-Ick Cha ◽  
Gary Green ◽  
Ram P. Naikawadi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Alveolar Epithelial

scholarly journals Inhibition of miR-199a-5p rejuvenates aged mesenchymal stem cells derived from patients with idiopathic pulmonary fibrosis and improves their therapeutic efficacy in experimental pulmonary fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linli Shi ◽  
Qian Han ◽  
Yimei Hong ◽  
Weifeng Li ◽  
Gencheng Gong ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Cellular Senescence ◽  
Therapeutic Efficacy ◽  
Sirtuin 1 ◽  
Ampk Signaling ◽  
Beneficial Effects ◽  
Age Related ◽  
Control Mscs

Abstract Background Idiopathic pulmonary fibrosis (IPF) is an age-related disease with no cure. Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy for IPF treatment. Nevertheless, MSCs derived from patients with IPF (IPF-MSCs) become senescent, thereby reducing their beneficial effects in IPF. MicroRNAs (miRNAs) mediate the senescence of MSCs, but the underlying mechanisms are not fully understood. We investigated the mechanisms by which miR-199a-5p regulates IPF-MSC senescence and whether its inhibition could rejuvenate IPF-MSCs and enhance their therapeutic efficacy. Methods Control-MSCs and IPF-MSCs were isolated from the adipose tissue of age-matched healthy and IPF donors, respectively. Cell senescence was examined by senescence-associated β-galactosidase (SA-β-gal) staining. The level of miR-199a-5p was measured by RT-PCR. Autophagy was determined using a transmission electron microscope (TEM). The therapeutic efficacy of anti-miR-199a-5p-IPF-MSCs was assessed using a mouse model of bleomycin-induced lung fibrosis. Results Despite similar surface makers, IPF-MSCs exhibited increased cellular senescence and decreased proliferative capacity compared with control-MSCs. The expression of miR-199a-5p was significantly enhanced in the serum of IPF patients and IPF-MSCs compared with that of healthy donors and control-MSCs. The upregulation of miR-199a-5p induced senescence of control-MSCs, whereas the downregulation rescued IPF-MSC senescence. Mechanistically, miR-155-5p suppressed autophagy of MSCs via the AMPK signaling pathway by downregulating the expression of Sirtuin 1(Sirt1), resulting in cellular senescence. Accordingly, miR-155-5p inhibition promoted autophagy and ameliorated IPF-MSC senescence by activating the Sirt1/AMPK signaling pathway. Compared with IPF-MSCs, the transplantation of anti-miR-199a-5p-IPF-MSCs increased the ability to prevent progression of pulmonary fibrosis in bleomycin-treated mice. Conclusions Our study shows that miR-199a-5p regulates MSC senescence in patients with IPF by regulating the Sirt1/AMPK signaling pathway and miR-199a-5p is a novel target to rejuvenate IPF-MSCs and enhance their beneficial effects.

scholarly journals Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Aging ◽  
2015 ◽  
Vol 7 (9) ◽  
pp. 664-672 ◽  
Author(s):  
Hagai Yanai ◽  
Albert Shteinberg ◽  
Ziv Porat ◽  
Arie Budovsky ◽  
Alex Braiman ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cellular Senescence ◽  
Lung Fibroblasts

scholarly journals Effects of the Cytoplasm and Mitochondrial Specific Hydroxyl Radical Scavengers TA293 and mitoTA293 in Bleomycin-Induced Pulmonary Fibrosis Model Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1398
Author(s):  
Takahiro Sakai ◽  
Hidetsugu Takagaki ◽  
Noriyuki Yamagiwa ◽  
Michio Ui ◽  
Shinichi Hatta ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Hydroxyl Radical ◽  
P38 Mapk ◽  
Cellular Senescence ◽  
Nlrp3 Inflammasome ◽  
Lung Fibrosis ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

Lung fibrosis is the primary pathology in idiopathic pulmonary fibrosis and is considered to result from an increase in reactive oxygen species (ROS) levels in alveolar epithelial cells. However, the exact mechanism underlying lung fibrosis remains unclear and there is no effective therapy. The hydroxyl radical (•OH) has the strongest oxidizing potential among ROS. Recently, •OH localized to the cytoplasm (cyto •OH) was reported to induce cellular senescence, while mitochondria-localized •OH (mt •OH) was reported to induce apoptosis. We developed the cyto •OH- and mt •OH-scavenging antioxidants TA293 and mitoTA293 to evaluate the effects of cyto •OH and mt •OH in a bleomycin (BLM)-induced pulmonary fibrosis model. Treatment of BLM-induced pulmonary fibrosis mice with TA293 suppressed the induction of cellular senescence and fibrosis, as well as inflammation in the lung, but mitoTA293 exacerbated these. Furthermore, in BLM-stimulated primary alveolar epithelial cells, TA293 suppressed the activation of the p-ATMser1981/p-p53ser15/p21, p-HRI/p-eIF2ser51/ATF4/p16, NLRP3 inflammasome/caspase-1/IL-1β/IL1R/p-p38 MAPK/p16, and p21 pathways and the induction of cellular senescence. However, mitoTA293 suppressed the induction of mitophagy, enhanced the activation of the NLRP3 inflammasome/caspase-1/IL1β/IL1R/p-p38 MAPK/p16 and p21 pathways, and exacerbated cellular senescence, inflammation, and fibrosis. Our findings may help develop new strategies to treat idiopathic pulmonary fibrosis.

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