Transforming growth factor-β1 and lung allograft fibrosis1

El‐Gamel, Adam; Awad, Mohammed; Sim, Ewan; Hasleton, Philip; Yonan, Nizar; Egan, Jim; Deiraniya, Abdul K.; Hutchinson, Ian V.

doi:10.1016/s1010-7940(98)00048-7

Cited by 63 publications

(2 citation statements)

References 11 publications

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“…11 In addition, homozygosity for 915 G was signi cantly more frequent in patients developing lung allograft brosis after transplantation. 28 In patients with chronic hepatitis C virus infection, a signi cant relationship between the homozygous 915 G genotype and development of progressive hepatic brosis was reported. 29 Consistent with these ndings, the patients with WHO class IV glomerulonephritis in our study were all homozygous for the 915 G allele.…”

Section: Discussionmentioning

confidence: 99%

The transforming growth factor-β1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

Schotte

Willeke

Rust

et al. 2003

Lupus

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Lymphocyte production of transforming growth factor (TGF)-beta1 is decreased in systemic lupus erythematosus (SLE). The lack of this immunoregulatory cytokine may contribute to the characteristic T cell disregulation and aberrant B cell stimulation in SLE patients. The less common C allele of the TGFB1 polymorphism (G915C) is associated with a lower TGF-beta1 production capacity. We performed a population-based case-control study to analyse the impact of this polymorphism on disease susceptibility, on clinical SLE manifestations and autoantibody production. A total of 203 German Caucasian SLE patients (fulfilling the 1982 ACR disease duration 11.5 +/- 7.0 years) and 158 ethnically, age- and sex-matched healthy controls were genotyped with a mutagenically separated polymerase chain reaction. There were no significant differences in the genotype distribution and allele frequencies between patients (915 C = 0.08) and healthy controls (915 C = 0.10). Comparing subgroups of patients, we found no association of major disease manifestations or specific autoantibodies with TGFB1 genotypes or alleles. The TGFB1 polymorphism (G915C) neither significantly contributes to the disease susceptibility, nor predisposes to clinical and immunological manifestations typical of SLE. Further studies are needed to corroborate the pathogenic role of TGF-beta1 in SLE patients and to identify the precise genetic elements controlling its production.

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Section: Discussionmentioning

confidence: 99%

The transforming growth factor-β1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

Schotte

Willeke

Rust

et al. 2003

Lupus

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“…This study reports novel ndings from a comparative proteomic analysis of TBBx tissue after LTx, which aimed to identify diagnostic biomarkers and molecular events to explain isolated histologic EOS in ammation and its relationship with ACR. (21). IHC analysis of 18 explanted lungs with RAS showed a signi cantly higher number of eosinophils per area in RAS lungs compared to BOS explants and controls (22).…”

Section: Discussionmentioning

confidence: 96%

Proteomic analysis of transbronchial biopsy tissue reveals a distinct proteome and mechanistic pathways in high-grade eosinophilic inflammation after lung transplantation

Tahmasbpour,

Philp,

Cree

et al. 2024

Preprint

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Background: Eosinophilic (EOS) inflammation is associated with acute cellular rejection (ACR) and an increased risk of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx); however, the underlying mechanisms remain unclear. We aimed to identify potential biomarkers and molecular mechanisms behind EOS inflammation after LTx. Methods: A cross-sectional comparative proteome analysis of transbronchial biopsy (TBBx) tissue was performed using formalin-fixed paraffin-embedded (FFPE) tissue from 18 LTx recipients. The cohort was comprised of isolated EOS inflammation (n=6), ACR (n=6) and these were compared with stable controls (n=6). EOS TBBx were defined as ≥10 eosinophil per high power field without ACR. ACR TBBx was defined as ISHLT A-grade >/=2. Control biopsies were defined as those without ACR, EOS or positive BAL microbiology at 120 days after LTx. Peptides were extracted from TBBx and subjected to liquid-chromatography mass spectrometry. Differentially expressed proteins (DEPs) were identified and quantified using bioinformatic tools and then candidate biomarkers validated by immunohistochemistry (IHC) staining. Results: Using a cut-off of Q<0.05 and a fold change of >1.6 for the variation in expression, 61 DEPs were identified in EOS TBBx, 56 of which were upregulated and 5 were downregulated. High-protein overlap (74.84%) was found between ACR and EOS groups. Several proteins such as Serpins, CFL-1, MIF, DDX3X, CCT8, Gal-3, Coro1A, Collagens and Mucins were upregulated in EOS TBBx. IHC staining validated alterations in the expression of target proteins. Bioinformatic analysis further revealed that most DEPs in EOS TBBx are related to leukocytes migration and activation, inflammasome formation, free radical production and oxidative stress, epithelial mesenchymal transition and excessive deposition of extracellular matrix. Conclusions: This study discovers and validates specific proteomic signatures that link EOS with ACR and elucidates mechanisms of injurious allograft inflammation. A number of novel therapeutic targets and potential early biomarkers are identified for allograft inflammation which require future diagnostic and prognostic validation.

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Acute Lung Injury

Beasley

2008

Dail and Hammar’s Pulmonary Pathology

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Transforming growth factor-β1 and lung allograft fibrosis1

Cited by 63 publications

References 11 publications

The transforming growth factor-β1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

The transforming growth factor-β1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus

Proteomic analysis of transbronchial biopsy tissue reveals a distinct proteome and mechanistic pathways in high-grade eosinophilic inflammation after lung transplantation

Acute Lung Injury

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