Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis

Kalafatis, Dimitrios; Löfdahl, Anna; Näsman, Per; Dellgren, Göran; Wheelock, Åsa M.; Rendin, Linda Elowsson; Sköld, Magnus; Westergren‐Thorsson, Gunilla

doi:10.3390/ijms222413421

Cited by 11 publications

(10 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies have confirmed that many proteins related to the acquired immune system, such as anti-heat shock protein- (HSP-) 70 antibodies [ 57 ], C-X-C motif chemokine 13 (CXCL13) [ 58 ], anti-vimentin antibodies [ 59 ], and some T-cell subpopulations, might be associated with worse prognosis, acute exacerbations, and pulmonary hypertension. Thus, these proteins could be used as objective biomarkers in the diagnosis of IPF.…”

Section: Discussionmentioning

confidence: 99%

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Zhao

Wang

et al. 2023

Journal of Immunology Research

View full text Add to dashboard Cite

Background. Idiopathic pulmonary fibrosis (IPF) is a disease with significant morbidity, progressive deterioration of lung function till death, and lack of effective treatment options. This study aims to explore the global research trends in IPF and immune response to predict the research hotspot in the future. Materials and methods. All related publications on IPF and immune response since the establishment of diagnostic criteria for IPF were retrieved using the Web of Science (WOS) database. VOSviewer, GraphPad Prism 6, CiteSpace version 5.6. R5 64-bit, and a bibliometrics online platform were used to extract and analyze the trends in relevant fields. Results. From March 1, 2000, to September 30, 2022, a total of 658 articles with 25,126 citations met the inclusion criteria. The United States ranked first in number of publications (n = 217), number of citations (n = 14,745), and H-index (62). China ranked second in publications (n = 124) and seventh and fifth for citation frequency and H-index, respectively. The American Journal of Respiratory and Critical Care Medicine (impact factor = 30.528) published the most articles in the field. The author Kaminski N. from the United States was the most influential author with 26 publications and an H-index of 24. Among the 52 keywords that co-occurred at least 20 times, the main keywords were concentrated in “Inflammation related” and “Biomarker related” clusters. “biomarker” (AAY 2018.64, 25 times) was a newly emerged keyword. Conclusions. The United States has an unequivocal advantage in IPF and immunization, but China shows a faster developing trend. The American Journal of Respiratory and Critical Care Medicine should be prioritized for leading articles. This study indicates that exploration of ideal immune-related biomarkers to provide evidence for the clinical work of IPF might be a hotspot in the near future.

show abstract

Section: Discussionmentioning

confidence: 99%

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Zhao

Wang

et al. 2023

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…In lung epithelial cells, MMP7 regulates β-catenin to promote wound healing and tissue remodelling [16] and is therefore necessary for homeostatic maintenance of tissue [17]. However, pathological epithelial cell dysfunction may occur later in the fibrogenic process, perhaps because of a dysregulated and fibrotic ECM, which is known to drive IPF pathology [18][19][20][21]. It is also possible that there is fibroblast-like cell which expresses MMP7 that drives honeycomb cyst formation.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis

et al. 2022

View full text Add to dashboard Cite

Introduction/AimIdiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) is a protein secreted by epithelial cells in IPF lungs. It is not known if MMP7 expression correlates with fibrotic changes in lung tissue.MethodsTissue samples from lung apices and bases were obtained from 20 IPF patients and 14 non-diseased control (NDC) donors. In formalin-fixed paraffin embedded (FFPE) sections, histological assessment of fibrosis was performed; overall MMP7 positivity was assessed by immunohistochemistry (IHC) and MMP7+ cells were quantified using multiplex IHC. Protein expression of MMP7 in whole lung lysates was quantified by western blotting. Bulk tissue transcriptomic profiles of 101 samples were analysed using RNA sequencing technologies.ResultsLung tissue from IPF bases was more fibrotic than in apices. MMP7 protein is elevated in IPF lung base tissue. In IPF whole lung lysates, MMP7 protein levels are increased compared to NDC donors and was increased in IPF lung bases compared to apices. MMP7 protein levels correlated with MMP7 gene expression levels in lung tissue. MMP7 transcript levels were increased in IPF base compared to NDC base lung tissue and increased in IPF base tissue compared to IPF apex tissue.ConclusionsOur cross-sectional study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially non-epithelial or immune cell source. Mechanisms of disease progression in IPF are still unclear and our study suggests aberrant MMP7 production may be a histological starting point of lung tissue fibrosis.

show abstract

“…These results are in good agreement with the recent PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study conclusions indicating that serum SP-D and MMP-7 could best differentiate between IPF patients and controls [139,140]. In addition, recent studies using a proximity extension assay identified higher protein levels of MMP-7, IL-6, NOS3 and CASP-8 in PF progressive patients compared to stable patients at follow-up, due to the importance of vascular and remodeling processes linked to progression of the disease [141]. However, recent studies question if MMP-7 is related to PF prognosis [35,142].…”

Section: Mmp-7mentioning

confidence: 99%

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

Chuliá-Peris

Carreres-Rey

Gabasa

et al. 2022

IJMS

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization, which have an impact on the biomechanical traits of the lung. In this context, the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is lost. Interestingly, several MMPs are overexpressed during PF and exhibit a clear profibrotic role (MMP-2, -3, -8, -11, -12 and -28), but a few are antifibrotic (MMP-19), have both profibrotic and antifibrotic capacity (MMP7), or execute an unclear (MMP-1, -9, -10, -13, -14) or unknown function. TIMPs are also overexpressed in PF; hence, the modulation and function of MMPs and TIMP are more complex than expected. EMMPRIN/CD147 (also known as basigin) is a transmembrane glycoprotein from the immunoglobulin superfamily (IgSF) that was first described to induce MMP activity in fibroblasts. It also interacts with other molecules to execute non-related MMP actions well-described in cancer progression, migration, and invasion. Emerging evidence strongly suggests that CD147 plays a key role in PF not only by MMP induction but also by stimulating fibroblast myofibroblast transition. In this review, we study the structure and function of MMPs, TIMPs and CD147 in PF and their complex crosstalk between them.

show abstract

Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis

Cited by 11 publications

References 94 publications

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Hotspots and Frontiers of Host Immune Response in Idiopathic Pulmonary Fibrosis: A Bibliometric and Scientific Visual Research from 2000 to 2022

Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

Contact Info

Product

Resources

About