scholarly journals C/EBPβ Acetylation is Involved in Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Jingzhu Zhou ◽  
Xiuhai Ji ◽  
yan fen ◽  
Hui ding
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Protein Expression ◽  
Western Blot ◽  
Real Time Pcr ◽  
Lung Fibrosis ◽  
Collagen I ◽  
Fibroblast Foci ◽  
The Relationship ◽  
Control Samples

Abstract Background: IPF is a progressive lung disease, characterized by excessive deposition of ECM. C/EBPβ is involved in the development of pulmonary fibrosis. However, the regulation of C/EBPβ in the context of pulmonary fibrosis is not clear. The study is to identify the C/EBPβ acetylation in IPF．Methods: Lung from six IPF and six control samples were selected in this study. We investigated the expression of C/EBPβ in lungs with Immunochemistry. Moreover, the expression of C/EBPβ mRNA via Real Time-PCR and its protein expression via Western Blot were performed. Meanwhile, the levels of collagen-I and α-SMA as markers of pulmonary fibrosis were also determined by Western Blot. Furthermore, we confirmed the relationship between α-SMA and acetylated C/EBPβ by Co-Immunoprecipitation. Results: We found the elevated C/EBPβ mostly locating in fibroblast foci in lungs of IPF. And the expression of C/EBPβ RNA and protein were obviously increased in IPF (P <0.05), in which the proteins of α-SMA and collagen-I were enhanced (P <0.05). Furthermore, the stronger acetylation of C/EBPβ binging to the α-SMA gene was shown in lung fibrosis (P <0.05). Conclusions: The increased expression of C/EBPβ acetylation associated with α-SMA expression is involved in the development of pulmonary fibrosis.

scholarly journals Changes in Neutrophil–Lymphocyte or Platelet–Lymphocyte Ratios and Their Associations with Clinical Outcomes in Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 10 (7) ◽  
pp. 1427
Author(s):  
Steven D. Nathan ◽  
Jayesh Mehta ◽  
John Stauffer ◽  
Elizabeth Morgenthien ◽  
Ming Yang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Clinical Outcomes ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Response To Treatment ◽  
Reference Ranges ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
The Relationship

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF.

scholarly journals Periplaneta Americana Extract may Attenuate 2,4,6-Trinitrobenzenesulfonic Acid-Induced Intestinal Fibrosis by Inhibiting TGF-β/Smad Signaling Pathway

2021 ◽  
Author(s):  
Jing Liu ◽  
Pin Lv ◽  
Xiang Rao ◽  
Jiajia Wang
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Periplaneta Americana ◽  
Collagen I ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway

Abstract PurposeIntestinal fibrosis is an incurable digestive disease accompanied by stricture formation, and it has an increasing incidence in recent years. Periplaneta americana is one of the medicinal insects with a long history. There are few reports on the effect of intestinal fibrosis. This study aims to evaluate the inhibitory effect of PA treatment on intestinal fibrosis. MethodsTNBS was used to establish intestinal fibrosis model by enema in BALB/c mice. The mice were treated with PA (50, 100, 200 mg/kg body weight) and 5-aminosalicylic acid (5-ASA) (40mg/kg) by gavage once a day for 6 weeks. At the end of the last week, the mice were sacrificed. Colon samples were collected for H&E and Masson staining. The mRNA and protein expression of α-smooth muscle actin (α-SMA), collagen I and the transforming growth factor-β (TGF-β) / Smad signaling pathway were conducted by real-time PCR and western blot analysis. In vitro, TGF-β1 was used to induce intestinal fibrosis at human colon fibroblasts (CCD-18Co). And using real-time PCR and western blot methods to detect the expression of α-SMA and collagen I. ResultsPA inhibited the expression of α-SMA and collagen I in vivo and in vitro. But the difference was that PA inhibited the TGF-β/Smad signaling pathway in vivo, and the same results had not been obtained in vitro. Conclusion: PA may attenuate intestinal fibrosis by inhibiting TGF-β/Smad signaling pathway, but more experiments were needed to prove it in vitro. ConclusionsPA has potential pharmacological effects in inhibiting intestinal fibrosis, and the TGF-β/Smad signaling pathway seemed promising.

scholarly journals Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 14 (1) ◽  
pp. 22-31
Author(s):  
Lisa Lancaster ◽  
Jonathan Goldin ◽  
Matthias Trampisch ◽  
Grace Hyun Kim ◽  
Jonathan Ilowite ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
Lung Fibrosis ◽  
Open Label ◽  
High Resolution Computed Tomography ◽  
Double Blind ◽  
Phase Iiib ◽  
Exploratory Data ◽  
Relative Change

Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied. Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF. Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory. Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: −9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: −1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were −14.2 mL and −83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: −8.7, 146.8]). Conclusion: Exploratory data suggest that in patients with IPF, 6 months’ treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.

NHLRC2 mRNA and protein expression in idiopathic pulmonary fibrosis

2021 ◽  
Author(s):  
Mervi Kreus ◽  
Siri Lehtonen ◽  
Johanna Salonen ◽  
Reetta Hinttala ◽  
Riitta Kaarteenaho
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Protein Expression ◽  
Mrna And Protein Expression

scholarly journals DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 938 ◽  
Author(s):  
Soo Jung Cho ◽  
Kyoung Sook Hong ◽  
Ji Hun Jeong ◽  
Mihye Lee ◽  
Augustine M. K. Choi ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Protein Expression ◽  
Alveolar Macrophages ◽  
Lung Inflammation ◽  
Mirna Biogenesis ◽  
Inflammasome Activation ◽  
Dependent Lung ◽  
Ribonuclease Iii ◽  
Primary Mouse

Idiopathic pulmonary fibrosis (IPF) has been linked to chronic lung inflammation. Drosha ribonuclease III (DROSHA), a class 2 ribonuclease III enzyme, plays a key role in microRNA (miRNA) biogenesis. However, the mechanisms by which DROSHA affects the lung inflammation during idiopathic pulmonary fibrosis (IPF) remain unclear. Here, we demonstrate that DROSHA regulates the absent in melanoma 2 (AIM2) inflammasome activation during idiopathic pulmonary fibrosis (IPF). Both DROSHA and AIM2 protein expression were elevated in alveolar macrophages of patients with IPF. We also found that DROSHA and AIM2 protein expression were increased in alveolar macrophages of lung tissues in a mouse model of bleomycin-induced pulmonary fibrosis. DROSHA deficiency suppressed AIM2 inflammasome-dependent caspase-1 activation and interleukin (IL)-1β and IL-18 secretion in primary mouse alveolar macrophages and bone marrow-derived macrophages (BMDMs). Transduction of microRNA (miRNA) increased the formation of the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks, which is required for AIM2 inflammasome activation in BMDMs. Our results suggest that DROSHA promotes AIM2 inflammasome activation-dependent lung inflammation during IPF.

The Relationship between Individual Histologic Features and Disease Progression in Idiopathic Pulmonary Fibrosis

2002 ◽  
Vol 166 (2) ◽  
pp. 173-177 ◽  
Author(s):  
Andrew G. Nicholson ◽  
Laura G. Fulford ◽  
Thomas V. Colby ◽  
Roland M. du Bois ◽  
David M. Hansell ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Disease Progression ◽  
The Relationship

scholarly journals Type-1 IFN primed monocytes in pathogenesis of idiopathic pulmonary fibrosis

2020 ◽  
Author(s):  
Emily Fraser ◽  
Laura Denney ◽  
Karl Blirando ◽  
Chaitanya Vuppusetty ◽  
Agne Antanaviciute ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Cells ◽  
Therapeutic Target ◽  
Lung Fibrosis ◽  
Ex Vivo ◽  
Treatment Options ◽  
Gene Expression Signature ◽  
Severe Form

ABSTRACTIdiopathic pulmonary fibrosis (IPF) is the most severe form of lung fibrosis. It is progressive, and has an extremely poor outcome and limited treatment options. The disease exclusively affects the lungs, and thus less attention has been focused on blood-borne immune cells. which could be a more effective therapeutic target than lung-based cells. Here, we questioned if circulating monocytes, which has been shown to be increased in IPF, bore abnormalities that might contribute to its pathogenesis. We found that levels of circulating monocytes correlated directly with the extent of fibrosis in the lungs, and increased further during acute clinical deterioration. Monocytes in IPF were phenotypically distinct, displaying increased expression of CD64, a type 1 IFN gene expression signature and a greater magnitude of type 1 IFN response when stimulated. These abnormalities were accompanied by markedly raised CSF-1 levels in the serum, prolonged survival of monocytes ex vivo, and increased numbers of monocytes in lung tissue. Our study defines the key monocytic abnormalities in IPF, proposing type 1 IFN-primed monocytes as a potential driver of an aberrant repair response and fibrosis. It provides a rationale for targeting monocytes and identifies monocytic CD64 as a potential specific therapeutic target for IPF.

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