https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45148 Wed 26 Oct 2022 19:13:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49742 Wed 26 Jun 2024 11:09:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31071 CLU−/−) mice persisted after bleomycin and it was associated with increased DNA damage, reduced DNA repair responses, and elevated cellular senescence. Remarkably, this pattern mirrored that observed in IPF lung tissues. Together, our results show that cellular localization of Clusterin leads to divergent effects on epithelial cell regeneration and lung repair during fibrosis.]]> Wed 24 Nov 2021 15:51:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45373 2O₂ or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients]]> Thu 27 Oct 2022 12:28:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39031 1 as have pericytes² and endothelial-mesenchymal transition.^3,4 However, the most studied mechanism is epithelial-mesenchymal transition (EMT), in which epithelial cells lose epithelial characteristics and become more mesenchymal, gaining mobility and enhanced ability to secrete ECM. This highly dynamic process has been subcategorized according to the three main functions it is associated with: embryonic development (type I), wound healing and tissue repair (type II), and cancer (type III). In this translational review, the mechanisms, roles, and impact of EMT (particularly type II) in chronic lung diseases are discussed. We also evaluate whether current medications influence EMT and how we may affect this process in the future.]]> Mon 29 Jan 2024 17:51:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35652 Mon 20 Nov 2023 11:12:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40195 Mon 08 Aug 2022 13:28:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46097 P < 0.05, n = 5–8). The targeting of cGAS also attenuated etoposide-induced senescence in Ctrl-LFs (P < 0.05, n = 5–8). Levels of mitochondrial DNA (mDNA) detected by qPCR in the cytosol and medium of IPF-LFs or senescence-induced Ctrl-LFs were higher than Ctrl-LFs at baseline (P < 0.05, n = 5–7). The addition of DNAse I (100 U/ml) deaccelerated IPF-LF senescence (P < 0.05, n = 5), whereas ectopic mDNA or the induction of endogenous mDNA release augmented Ctrl-LF senescence in a cGAS-dependent manner (P < 0.05, n = 5). In conclusion, we provide evidence that cGAS reinforces lung fibroblast senescence involving damaged self DNA. The targeting of cGAS to supress senescent-like responses may have potential important therapeutic implications in the treatment of IPF.]]> Fri 11 Nov 2022 11:23:00 AEDT ]]>