Progranulin and Activin A Concentrations are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Xie, Tian; Han, Lizhen; Chen, Yongxing; Wu, Haihong

doi:10.1007/s00408-021-00470-6

Cited by 10 publications

(9 citation statements)

References 21 publications

(34 reference statements)

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“…Remarkably, like MMP7, levels of activin A, eotaxin, MCP1, MDC, and PARC were also significantly associated with lung P16 expression and the LASSO regression designated activin A as the most important predictor. A recent study found increased circulating levels of activin A in persons with acute exacerbation of IPF compared to those with stable IPF and, similar to our study, evidenced a significant negative correlation with DLCO [28]. As our data would suggest, the plasma concentration of activin A is an important predictor of lung senescent cell burden, an interesting future direction would be to explore the contribution of senescent cells and the SASP to acute IPF exacerbation.…”

Section: Discussionsupporting

confidence: 88%

Biomarkers of cellular senescence in idiopathic pulmonary fibrosis

et al. 2023

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Background Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes. Methods We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes. Results The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16. Conclusions Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.

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Section: Discussionsupporting

confidence: 88%

Biomarkers of cellular senescence in idiopathic pulmonary fibrosis

et al. 2023

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“…PGRN, as a pleiotropic growth factor, has been shown to mediate immune response and tissue regeneration in addition to many other biological processes. It was shown to be involved in the pathogenesis of liver fibrosis [14], acute ILD associated with DM [13] and its role has been even raised in acute exacerbation of IPF according to a small single-center study [15], but its potential function in other ILDs has not yet been examined.…”

Section: Discussionmentioning

confidence: 99%

Serum Progranulin Level Might Differentiate Non-IPF ILD from IPF

Tóth

Müller

Nagy

et al. 2023

IJMS

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Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.

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“…A number of studies have implicated activin A overexpression in the development of fibrosis [ 63 , 64 ]. While the impaired systolic strain is linked to increased fibrosis [ 65 ], few studies investigated the direct relationship between activin A overexpression and the development of cardiac fibrosis, and whether this effect could be ameliorated by inhibition of activin A receptors. Hu et al showed that activin A stimulates cardiac fibroblast proliferation and differentiation [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction

Bakrania

Palei

Bhattarai

et al. 2022

Cells

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Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25–6 µg/day) on a gestational day (GD) 14 (n = 6–10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, p < 0.01) was associated with impaired GLS (Sham: −22.1 ± 0.8%, 6 µg/day: −14.7 ± 1.14%, p < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction.

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Progranulin and Activin A Concentrations are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Cited by 10 publications

References 21 publications

Biomarkers of cellular senescence in idiopathic pulmonary fibrosis

Biomarkers of cellular senescence in idiopathic pulmonary fibrosis

Serum Progranulin Level Might Differentiate Non-IPF ILD from IPF

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction

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