Dataset Information

Pulmonary microvascular endothelial cells support alveolar epithelial growth via bone morphogenetic protein 6 secretion

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and emphysema development, associated with enhanced tissue destruction and defective repair. Supporting cells in the alveolar niche play a crucial role in guiding the activation of alveolar epithelial progenitor cells during repair. Despite their close anatomical proximity, understanding of the supportive role of the pulmonary microvascular endothelium in adult alveolar epithelial repair remains limited. We hypothesized that angiocrine factors secreted by pulmonary endothelial cells support alveolar epithelial cell growth. Here, we report that human pulmonary microvasculature endothelial cells (HPMECs) support murine and human alveolar organoid formation through paracrine signaling via the secretion of extracellular vesicles and soluble factors. Transcriptomic and proteomic analysis pinpointed HPMEC-derived bone morphogenetic protein 6 (BMP6) as a critical factor for alveolar organoid formation. BMP6 deficiency was associated with reduced Wnt signaling and augmented oxidative stress signaling in murine lung tissue. Furthermore, BMP6 promoted alveolar epithelial cell growth, whereas function-blocking antibodies targeting BMP6 inhibited the beneficial effect of endothelial cells on murine alveolar organoid formation. Taken together, our findings highlight BMP6 as a key regulator of adult epithelial repair and suggest its potential as a therapeutic target for lung repair, particularly in individuals with COPD.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell

DISEASE(S): Chronic Obstructive Pulmonary Disease

SUBMITTER: Justina Clarinda Wolters

LAB HEAD: Justina Clarinda Wolters

PROVIDER: PXD053755 | Pride | 2026-07-02

REPOSITORIES: Pride

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Pulmonary Microvascular Endothelial Cells Support Alveolar Epithelial Growth via Bone Morphogenetic Protein 6 Secretion.

van der Koog Luke L Wu Xinhui X Nugraha Dyan F DF Ravi Abilash A Wolters Justina C JC Verhamme Fien M FM Horvatovich Peter L PL Bracke Ken R KR van der Does Anne M AM Hiemstra Pieter S PS Johnson Jill R JR Harmsen Martin C MC Nagelkerke Anika A Gosens Reinoud R

American journal of respiratory cell and molecular biology 20251201 6

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and emphysema development, associated with enhanced tissue destruction and defective repair. Supporting cells in the alveolar niche play a crucial role in guiding the activation of alveolar epithelial progenitor cells during repair. Despite their close anatomical proximity, understanding of the supportive role of the pulmonary microvascular endothelium in adult alveolar epithelial repair remains limit ...[more]

PMID: 40439543

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