https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45148 Wed 26 Oct 2022 19:13:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49742 Wed 26 Jun 2024 11:09:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45701 Tue 28 Mar 2023 15:44:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47798 Tue 28 Mar 2023 15:16:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54219 ACTA2), collagen (COL) 1A1 and fibulin-1 (Fbln1) and higher Fbln1 protein deposition after 7 days. Our results show that exposure of lung fibroblasts to fibrotic stiffness activates genes and secreted factors that are part of fibrotic responses and part of the Senescence-associated secretory phenotype (SASP). This overlap may contribute to the creation of a feedback loop whereby fibroblasts create a perpetuating cycle reinforcing progression of a fibrotic response.]]> Tue 13 Feb 2024 11:58:49 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48871 Thu 13 Apr 2023 12:47:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44052 Thu 06 Oct 2022 08:58:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35652 Mon 20 Nov 2023 11:12:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42174 2⁻) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated β-galactosidase accumulation, and restored normal mitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated.]]> Fri 26 Aug 2022 08:10:19 AEST ]]> https://nova.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 ]]>