https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45148 Wed 26 Oct 2022 19:13:19 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49742 Wed 26 Jun 2024 11:09:03 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:25846 Wed 21 Aug 2024 11:12:20 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48369 Fbln1c-deficient (Fbln1c^–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target.]]> Wed 15 Mar 2023 13:12:38 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:41157 Wed 15 Feb 2023 10:57:18 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22104 in vitro measures of fibrosis: cell attachment, proliferation and viability, and ECM deposition, were examined. Among these peptides, peptide 1C1 (FBLN1C1) enhanced ASM cell and fibroblast attachment. FBLN1C1 increased mitochondrial activity and proliferation in fibroblasts. In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups. Peptides FBLN1C2 to FBLN1C7 had no activity. The active fibulin-1C peptide identified in this study describes a useful tool for future studies. Ongoing investigation of the role of fibulin-1 may reveal the mechanisms underlying the pathphysiology of chronic lung diseases.]]> Wed 11 Apr 2018 16:41:15 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22587 0.75, n=7), and healthy controls (HC) (n=9) were stimulated with bacterial (LPS (1 g/mL), fMLF (100 nM)), and viral (imiquimod (3 g/mL), R848 (1.5 g/mL), and poly I:C (10 g/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release. Results: Constitutive NE was enhanced in AGood neutrophils compared to HC. fMLF stimulated neutrophils from ASubopt but not AGood produced 50% of HC levels. fMLF induced MMP-9 was impaired in ASubopt and AGood compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1 and FEV1/FVC. ASubopt and AGood responded similarly to other stimuli. Conclusions: Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.]]> Wed 11 Apr 2018 14:23:49 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30281 Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-a, IL-33, and CXCL1) in experimental COPD. Fbln1c⌿ mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.]]> Wed 11 Apr 2018 13:33:47 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:9558 Wed 11 Apr 2018 12:40:26 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:21292 in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined using a murine model of chronic OVA-induced allergic airways disease. Results: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. Conclusion: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.]]> Wed 11 Apr 2018 11:14:04 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45701 Tue 28 Mar 2023 15:44:53 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24139 Tue 20 Aug 2024 09:26:27 AEST ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44253 Tue 11 Oct 2022 12:28:35 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33793 –/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild‐type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c^–/– mice with AAD also had reduced numbers of α‐smooth muscle actin‐positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)‐5, IL‐13, IL‐33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL‐5, IL‐33 and TNF levels in lung‐draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3‐positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL‐5 and IL‐13 from co‐cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium‐treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma.]]> Thu 28 Oct 2021 13:02:39 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33903 Thu 24 Mar 2022 11:29:04 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48871 Thu 13 Apr 2023 12:47:57 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44052 Thu 06 Oct 2022 08:58:07 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:11251 Sat 24 Mar 2018 08:10:53 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:19841 Sat 24 Mar 2018 07:57:07 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:35652 Mon 20 Nov 2023 11:12:20 AEDT ]]> https://novaprd-lb.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 ]]>