scholarly journals PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Andrea Doni ◽  
Alberto Mantovani ◽  
Barbara Bottazzi ◽  
Remo Castro Russo
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Life Quality ◽  
Unknown Origin ◽  
Protective Role

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

The Role of Proteinase-activated Receptor-2 in Idiopathic Pulmonary Fibrosis: Is There Really Novel Therapeutic Potential Here?

2012 ◽  
Vol 185 (4) ◽  
pp. 459-460
Author(s):  
Malgorzata Wygrecka ◽  
Grazyna Kwapiszewska ◽  
Ewa Jablonska ◽  
Susanne von Gerlach ◽  
Ingrid Henneke ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Novel Therapeutic

scholarly journals A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

2017 ◽  
Vol 26 (144) ◽  
pp. 160125 ◽  
Author(s):  
Gianluca Bagnato ◽  
William Neal Roberts ◽  
Jesse Roman ◽  
Sebastiano Gangemi
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Therapeutic Potential ◽  
Messenger Rnas ◽  
Rna Sequences ◽  
Non Coding Rna ◽  
Evolutionarily Conserved

Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20–23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential.

scholarly journals Protective Role of the Nucleic Acid Sensor STING in Pulmonary Fibrosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Florence Savigny ◽  
Corinne Schricke ◽  
Norinne Lacerda-Queiroz ◽  
Mélanie Meda ◽  
Mégane Nascimento ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Protective Role ◽  
Type I ◽  
Danger Signals ◽  
Limited Efficacy ◽  
Nucleic Acid Sensor ◽  
Type Iii Interferon ◽  
Severe Type

Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of interstitial lung disease for which current treatments display limited efficacy. IPF is largely driven by host-derived danger signals released upon recurrent local tissue damage. Here we explored the roles of self-DNA and stimulator of interferon genes (STING), a protein belonging to an intracellular DNA sensing pathway that leads to type I and/or type III interferon (IFN) production upon activation. Using a mouse model of IPF, we report that STING deficiency leads to exacerbated pulmonary fibrosis with increased collagen deposition in the lungs and excessive remodeling factors expression. We further show that STING-mediated protection does not rely on type I IFN signaling nor on IL-17A or TGF-β modulation but is associated with dysregulated neutrophils. Together, our data support an unprecedented immunoregulatory function of STING in lung fibrosis.

scholarly journals Alveolar Epithelial Type II Cells as Drivers of Lung Fibrosis in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 21 (7) ◽  
pp. 2269 ◽  
Author(s):  
Tanyalak Parimon ◽  
Changfu Yao ◽  
Barry R Stripp ◽  
Paul W Noble ◽  
Peter Chen
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Heterogeneous Population ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Number Of Factors ◽  
Normal Functional

: Alveolar epithelial type II cells (AT2) are a heterogeneous population that have critical secretory and regenerative roles in the alveolus to maintain lung homeostasis. However, impairment to their normal functional capacity and development of a pro-fibrotic phenotype has been demonstrated to contribute to the development of idiopathic pulmonary fibrosis (IPF). A number of factors contribute to AT2 death and dysfunction. As a mucosal surface, AT2 cells are exposed to environmental stresses that can have lasting effects that contribute to fibrogenesis. Genetical risks have also been identified that can cause AT2 impairment and the development of lung fibrosis. Furthermore, aging is a final factor that adds to the pathogenic changes in AT2 cells. Here, we will discuss the homeostatic role of AT2 cells and the studies that have recently defined the heterogeneity of this population of cells. Furthermore, we will review the mechanisms of AT2 death and dysfunction in the context of lung fibrosis.

scholarly journals Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-216882
Author(s):  
Amit Kumar ◽  
Evan Elko ◽  
Sierra R Bruno ◽  
Zoe F Mark ◽  
Nicolas Chamberlain ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Therapeutic Potential ◽  
Lung Parenchyma ◽  
Secretory Protein ◽  
Club Cell ◽  
Club Cells ◽  
Research Consortium ◽  
Related Proteins

BackgroundThe role of club cells in the pathology of idiopathic pulmonary fibrosis (IPF) is not well understood. Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum-based redox chaperone required for the functions of various fibrosis-related proteins; however, the mechanisms of action of PDIA3 in pulmonary fibrosis are not fully elucidated.ObjectivesTo examine the role of club cells and PDIA3 in the pathology of pulmonary fibrosis and the therapeutic potential of inhibition of PDIA3 in lung fibrosis.MethodsRole of PDIA3 and aberrant club cells in lung fibrosis was studied by analyses of human transcriptome dataset from Lung Genomics Research Consortium, other public resources, the specific deletion or inhibition of PDIA3 in club cells and blocking SPP1 downstream of PDIA3 in mice.ResultsPDIA3 and club cell secretory protein (SCGB1A1) signatures are upregulated in IPF compared with control patients. PDIA3 or SCGB1A1 increases also correlate with a decrease in lung function in patients with IPF. The bleomycin (BLM) model of lung fibrosis showed increases in PDIA3 in SCGB1A1 cells in the lung parenchyma. Ablation of Pdia3, specifically in SCGB1A1 cells, decreases parenchymal SCGB1A1 cells along with fibrosis in mice. The administration of a PDI inhibitor LOC14 reversed the BLM-induced parenchymal SCGB1A1 cells and fibrosis in mice. Evaluation of PDIA3 partners revealed that SPP1 is a major interactor in fibrosis. Blocking SPP1 attenuated the development of lung fibrosis in mice.ConclusionsOur study reveals a new relationship with distally localised club cells, PDIA3 and SPP1 in lung fibrosis and inhibition of PDIA3 or SPP1 attenuates lung fibrosis.

Role of Wnt/PCP pathway on bronchial cell function in Idiopathic Pulmonary Fibrosis

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
S Barkha ◽  
M Gegg ◽  
H Lickert ◽  
M Königshoff
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Function

Role of Bcl-xL in hepatocyte growth factor-elicited epithelial protection in idiopathic pulmonary fibrosis

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
S Skwarna ◽  
I Henneke ◽  
W Seeger ◽  
T Geiser ◽  
A Günther ◽  
...  
Keyword(s):  
Growth Factor ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth
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