Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9

Oatis, Daniela; Simon-Repolski, Erika; Baltă, Cornel; Mihu, Alin; Pieretti, Gorizio; Alfano, Roberto; Peluso, Luisa; Trotta, Maria Consiglia; D’Amico, Michele

doi:10.3390/ijms23158210

Cited by 19 publications

(18 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the rapidly evolving COVID-19 pandemic, Gas6/TAM axis activation has gained interest due to its involvement in inflammatory responses and subsequent fibrosis, two features strictly related to severe SARS-CoV-2 clinical manifestations [ 28 ].…”

Section: Physiological Role Of the Gas6/tam Axis: An Overviewmentioning

confidence: 99%

“…A fine and timely regulation of fibrotic response is necessary to support physiological wound healing: as discussed for inflammation, also in the case of fibrosis, a de-regulated response could result in a negative clinical evolution, with diffuse fibrosis impairing the physiological activities of the involved tissues. In particular, fibrosis is triggered by virtually all types of insults and affects all organs and tissues [ 28 , 36 ]. Moreover, in virtually all progressive chronic diseases, fibrosis becomes irreversible over time, thus accounting for a progressive loss of functionality of the involved tissue [ 37 , 38 ].…”

Section: Gas6/tam Axis Role In Modulating Fibrotic Evolutionmentioning

confidence: 99%

See 1 more Smart Citation

Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients

Rizzi

Tonello

D’Onghia

et al. 2023

IJMS

View full text Add to dashboard Cite

Gas6 (growth arrest-specific gene 6) is a widely expressed vitamin K-dependent protein that is involved in many biological processes such as homeostatic regulation, inflammation and repair/fibrotic processes. It is known that it is the main ligand of TAMs, a tyrosine kinase receptor family of three members, namely MerTK, Tyro-3 and Axl, for which it displays the highest affinity. Gas6/TAM axis activation is known to be involved in modulating inflammatory responses as well as fibrotic evolution in many different pathological conditions. Due to the rapidly evolving COVID-19 pandemic, this review will focus on Gas6/TAM axis activation in SARS-CoV-2 infection, where de-regulated inflammatory responses and fibrosis represent a relevant feature of severe disease manifestation. Furthermore, this review will highlight the most recent scientific evidence supporting an unsuspected role of Axl as a SARS-CoV-2 infection driver, and the potential therapeutic advantages of the use of existing Axl inhibitors in COVID-19 management. From a physiological point of view, the Gas6/TAM axis plays a dual role, fostering the tissue repair processes or leading to organ damage and loss of function, depending on the prevalence of its anti-inflammatory or profibrotic properties. This review makes a strong case for further research focusing on the Gas6/TAM axis as a pharmacological target to manage different disease conditions, such as chronic fibrosis or COVID-19.

show abstract

Section: Physiological Role Of the Gas6/tam Axis: An Overviewmentioning

confidence: 99%

Section: Gas6/tam Axis Role In Modulating Fibrotic Evolutionmentioning

confidence: 99%

Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients

Rizzi

Tonello

D’Onghia

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The correlation of N-cleaved-Gal9 levels with sIL-2R levels in the recovery phase may indicate an involvement of cleaved-Gal-9 in persistent inflammation. Gal-9 can be implicated in the process of post-ARDS lung fibrosis in COVID-19 [ 48 ]. However, we observed that the patients did not present pulmonary fibrosis after TCZ treatment in this study.…”

Section: Discussionmentioning

confidence: 99%

Plasma N-Cleaved Galectin-9 Is a Surrogate Marker for Determining the Severity of COVID-19 and Monitoring the Therapeutic Effects of Tocilizumab

Iwasaki-Hozumi

Maeda

Niki

et al. 2023

IJMS

View full text Add to dashboard Cite

Galectin-9 (Gal-9) is known to contribute to antiviral responses in coronavirus disease 2019 (COVID-19). Increased circulating Gal-9 in COVID-19 is associated with COVID-19 severity. In a while, the linker-peptide of Gal-9 is susceptible to proteolysis that can cause the change or loss of Gal-9 activity. Here, we measured plasma levels of N-cleaved-Gal9, which is Gal9 carbohydrate-recognition domain at the N-terminus (NCRD) with attached truncated linker peptide that differs in length depending on the type of proteases, in COVID-19. We also investigated the time course of plasma N-cleaved-Gal9 levels in severe COVID-19 treated with tocilizumab (TCZ).. As a result, we observed an increase in plasma N-cleaved-Gal9 levels in COVID-19 and its higher levels in COVID-19 with pneumonia compared to the mild cases (healthy: 326.1 pg/mL, mild: 698.0 pg/mL, and with pneumonia: 1570 pg/mL). N-cleaved-Gal9 levels were associated with lymphocyte counts,C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R), D-dimer, and ferritin levels, and ratio of percutaneous oxygen saturation to fraction of inspiratory oxygen (S/F ratio) in COVID-19 with pneumonia and discriminated different severity groups with high accuracy (area under the curve (AUC): 0.9076). Both N-cleaved-Gal9 and sIL-2R levels were associated with plasma matrix metalloprotease (MMP)-9 levels in COVID-19 with pneumonia. Furthermore, a decrease in N-cleaved-Gal9 levels was associated with a decrease of sIL-2R levels during TCZ treatment. N-cleaved-Gal9 levels showed a moderate accuracy (AUC: 0.8438) for discriminating the period before TCZ from the recovery phase. These data illustrate that plasma N-cleaved-Gal9 is a potential surrogate marker for assessing COVID-19 severity and the therapeutic effects of TCZ.

show abstract

“…Likewise, Gal-8 has also been suggested to have disparate roles in immunity, functioning as an enhancer of the expression and secretion of many pro-inflammatory cytokines or as a cytokinebinding partner to sequester and hinder cytokine activity (12). For this reason, galectins have been linked to a variety of inflammatorydriven disorders (e.g., cancer, cardiovascular, and metabolic diseases) (11)(12)(13)(14)(15)(16). Moreover, since these molecules are also involved in pro-fibrotic processes (13), their role is particularly relevant because they are involved in the pathogenesis of several disorders affecting several organs including the heart and lungs (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, galectins have been linked to a variety of inflammatorydriven disorders (e.g., cancer, cardiovascular, and metabolic diseases) (11)(12)(13)(14)(15)(16). Moreover, since these molecules are also involved in pro-fibrotic processes (13), their role is particularly relevant because they are involved in the pathogenesis of several disorders affecting several organs including the heart and lungs (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

BackgroundGalectins are an eleven-member class of lectins in humans that function as immune response mediators and aberrancies in their expression are commonly associated with immunological diseases. Several studies have focused on galectins as they may represent an important biomarker and a therapeutic target in the fight against COVID-19. This systematic review and meta-analysis examined the usefulness of clinical assessment of circulating galectin levels in patients with COVID-19.MethodsInternational databases including PubMed, Scopus, Web of Science, and Embase were systematically used as data sources for our analyses. The random-effect model was implemented to calculate the standardized mean difference (SMD) and a 95% confidence interval (CI).ResultsA total of 18 studies, comprising 2,765 individuals, were identified and used in our analyses. We found that Gal-3 is the most widely investigated galectin in COVID-19. Three studies reported significantly higher Gal-1 levels in COVID-19 patients. Meta-analysis revealed that patients with COVID-19 had statistically higher levels of Gal-3 compared with healthy controls (SMD 0.53, 95% CI 0.10 to 0.96, P=0.02). However, there was no significant difference between severe and non-severe cases (SMD 0.45, 95% CI -0.17 to 1.07, P=0.15). While one study supports lower levels of Gal-8 in COVID-19, Gal-9 was measured to be higher in patients and more severe cases.ConclusionOur study supports Gal-3 as a valuable non-invasive biomarker for the diagnosis and/or prognosis of COVID-19. Moreover, based on the evidence provided here, more studies are needed to confirm a similar diagnostic and prognostic role for Gal-1, -8, and -9.

show abstract

Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9

Cited by 19 publications

References 112 publications

Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients

Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients

Plasma N-Cleaved Galectin-9 Is a Surrogate Marker for Determining the Severity of COVID-19 and Monitoring the Therapeutic Effects of Tocilizumab

Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis

Contact Info

Product

Resources

About