Biology subjects

Tufvesson, E.

Publications and source records attributed to Tufvesson, E..

3 recordsLinked to original sources

bioRxiv2026

Altered cellular VEGF dynamics in Chronic Obstructive Pulmonary Disease

Pulmonary vascular remodelling is common in patients with chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factors (VEGFs) are key mediators in angiogenesis and vascular remodelling and exist in different isoforms. VEGF-A is the most potent angiogenic member binding to VEGF receptor 2 (VEGFR2). There are, however, few studies on other isoforms, as VEGF-C, and its receptor VEGFR3 in COPD and subsequent impact of cAMP therapies on VEGF isoforms. Our aim was to evaluate the VEGF isoform synthesis in primary distal lung fibroblasts from control subjects (non-smokers (n=6) and ex-smokers (n=4), and COPD subjects with GOLD stage II (n=4) or GOLD stage IV (n=6), and the expression of VEGFR2 and VEGFR3 in human lung tissue. Primary lung fibroblasts were exposed to the cAMP generating therapies formoterol, iloprost, or roflumilast, the adenylyl cyclase activator forskolin or to transforming growth factor (TGF)-b1. VEGF isoforms were evaluated with ELISA. VEGF-C release was not significantly altered by TGF-{beta}1, in contrast to the increased levels of VEGF-A, in all fibroblasts. VEGF-C was significantly decreased by iloprost, forskolin and formoterol, whereas VEGF-A was significantly increased by iloprost and forskolin, with differences in release pattern between and within fibroblasts from control and COPD subjects. Exposure to VEGF-C specifically towards VEGFR3 decreased proliferative rate in human lung fibroblasts and bronchial epithelial cells. VEGFR2 and VEGFR3 were both present in parenchymal lung tissue and VEGFR2 in pulmonary blood vessels. in both healthy and COPD, whereas there was elevated expression of VEGFR3 in bronchial epithelium. In conclusion, TGF-{beta}1 and cAMP generating compounds have significant effects on VEGF-C and VEGF-A synthesis, which appear dysregulated in lung fibroblasts from ex-smokers and patients with COPD. Increased VEGFR3 expression in the bronchial epithelium in lung tissue, and studies into their functional impact, warrants further investigations.

pathology↗

bioRxiv2026

High-plex protein profiling on cytospin slides with bronchoalveolar lavage cells from asthma and COPD

Protein profiling of whole cells can accurately define cell subsets specific to disease identity and/or severity. Preserving whole cells on cytospin slides is common practice but is often used only for differential counts. Here we ran two studies and successfully applied a high-plex protein panel using the NanoString GeoMx, quantifying up to 47 proteins (of immune, cell death, and MAPK signalling markers) in bronchoalveolar lavage (BAL) cytospins from the four major cell types: macrophages, neutrophils, type-2 granulocytes and lymphocytes. Despite the small sample size for this feasibility study, several significant differences between disease and controls within several BAL cell types for both the asthma cohort (n=21) and the COPD cohort (n=20) were found. Overall, we believe applying this method can maximise biomarker discover of any precious preserved cytospin clinical samples and that the significant disease specific cell subsets discovered during the method testing are worthy of future investigation.

immunology↗

bioRxiv2025

Transcriptional Roadmap of the Human Airway Epithelium Identifying HLF as a Novel Regulator of Basal Stem Cell Function

RationaleThe human airway epithelium depends on a coordinated hierarchy of stem-and differentiated cells to maintain tissue integrity and respond to injury. Defining the transcriptional and translational programs that govern these processes is critical for understanding airway disease and advancing regenerative therapies. ObjectivesTo map the transcriptional landscape of the human airway epithelium and identify regulatory factors controlling basal stem cell function and epithelial differentiation. MethodsWe performed single-cell RNA sequencing on bronchial biopsies from nine healthy never-smokers, categorized into young (<40 years) and aged (>60 years) cohorts. Unbiased cell type annotation and pseudotime trajectory analysis were used to define cell states and transcription factor dynamics. Measurements and Main ResultsAll major airway epithelial cell types were identified, with conserved composition and transcriptional programs across age groups. Basal stem cells (BSCs) exhibited elevated ribosomal gene expression, indicating increased translational readiness. Pseudotime analysis revealed transitions from basal to differentiated states, with MYC, JUN, and FOS upregulated in proliferative suprabasal cells. HLF emerged as a BSC-enriched transcription factor downregulated upon differentiation. Functional assays showed that HLF overexpression suppresses proliferation in airway BSC and in lung squamous carcinoma cells, while Hlf-deficient mice display basal cell hyperplasia and deficient differentiation. In lung cancer datasets, low HLF expression correlated with worse patient survival. ConclusionsThis study defines conserved gene programs in the human airway epithelium and identifies HLF as a novel regulator of BSC proliferation and potential tumor suppressor. These findings may inform the development of regenerative therapies and contribute to improved understanding and treatment of lung disease.

molecular biology↗