Schleuter, H. | Search bioRxiv

bioRxiv2024

JUNB O-GlcNAcylation-mediated promoter accessibility of metabolic genes modulates distinct epithelial lineage in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with substantial unmet medical needs. While aberrant epithelial remodelling is a key factor in IPF progression, the molecular mechanisms behind this process remain elusive. Using a patient-derived 3D distal airway epithelial organoid model, we successfully recapitulate important IPF features, including the emergence of aberrant KRT5+/COL1A1+ basal cells and a metabolic shift towards increased O-linked {beta}-N-acetylglucosamine (O-GlcNAc) levels. Consistent with this, single-cell analysis of accessible chromatin reveals an increased chromatin accessibility in these aberrant basal cells, particularly at JUNB motif-enriched promoter regions of metabolic genes. O-GlcNAcylation shapes JUNB function and promotes a pro-fibrotic response to chronic injury, leading to aberrant epithelial remodelling. Site-specific deletion of O-GlcNAcylation on JUNB attenuates the metaplastic differentiation of basal cells, thereby aiding in the restoration of the alveolar lineage. Together, these data establish a novel link between metabolic dysregulation, mediated by the O-GlcNAc-JUNB axis, and bronchiolization in IPF, offering new therapeutic strategies to treat this fatal disease.

cell biology↗

bioRxiv2020

A systematic review of European farmer and non-farmer attitudes towards landscapes, ecosystem services, and agricultural management practices: Implications for permanent grassland management.

Permanent grassland (PG) is an important agricultural land use for the delivery of multiple ecosystem services (ES), including carbon sequestration, water quality protection, food production, habitat provision, and cultural activities. However, PG environments are threatened by sub-optimal management, cultivation, and abandonment that are influenced by context, land managers attitudes and societal demand for ES. Therefore, the perceptions and attitudes of key decision-makers (farmers) and other stakeholders (non-farmers, including citizens and consumers of the products of permanent grasslands, and ES) need to be understood to ensure the sustainability of PGs and the ES they provide. A systematic review of the literature identified 135 scholarly articles. Application of thematic analysis, allowed the organization, and synthesis of current research related to (different) stakeholder attitudes, and how these influence PG management and the delivery of ES. The results suggest that different stakeholders hold different views towards permanent grassland, with farmers in particular having to balance economic with other (potentially conflicting) drivers. The types of knowledge held by different groups of stakeholders, access to sources of information, as well as the influence of knowledge on behaviour; and environmental values (for example in relation to aesthetics or conservation of biodiversity) explained why certain motivations for attitudes and behaviours are held. A major gap, however, was identified in relation to PG as opposed to other types of landscape.

ecology↗