Khan Petra, Fytianos Kleanthis, Blumer Sabrina, Roux Julien, Gazdhar Amiq, Savic Spasenija, Knudsen Lars, Jonigk Danny, Kuehnel Mark P, Mykoniati Sofia, Tamm Michael, Geiser Thomas, Hostettler Katrin E
Department of Biomedicine and Clinics of Respiratory Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Pulmonary Medicine, University Hospital Bern, and Department of Biomedical Research, University of Bern, Bern, Switzerland.
Front Bioeng Biotechnol. 2022 Mar 8;10:844119. doi: 10.3389/fbioe.2022.844119. eCollection 2022.
In idiopathic pulmonary fibrosis (IPF), basal-like cells are atypically present in the alveolar region, where they may affect adjacent stromal cells by paracrine mechanisms. We here aimed to confirm the presence of basal-like cells in peripheral IPF lung tissue , to culture and characterize the cells and to investigate their paracrine effects on IPF fibroblasts and in bleomycin-injured rats . Basal-like cells are mainly localized in areas of pathological bronchiolization or honeycomb cysts in peripheral IPF lung tissue. Single-cell RNA sequencing (scRNA-seq) demonstrated an overall homogeneity, the expression of the basal cell markers cytokeratin KRT5 and KRT17, and close transcriptomic similarities to basal cells in the majority of cells cultured . Basal-like cells secreted significant levels of prostaglandin E2 (PGE2), and their conditioned medium (CM) inhibited alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1) and upregulated matrix metalloproteinase-1 (MMP-1) and hepatocyte growth factor (HGF) by IPF fibroblasts . The instillation of CM in bleomycin-injured rat lungs resulted in reduced collagen content, improved lung architecture, and reduced α-SMA-positive cells. Our data suggested that basal-like cells may limit aberrant fibroblast activation and differentiation in IPF through paracrine mechanisms.
在特发性肺纤维化（IPF）中，基底样细胞异常出现在肺泡区域，在该区域它们可能通过旁分泌机制影响相邻的基质细胞。我们的目的是确认IPF外周肺组织中基底样细胞的存在，培养并鉴定这些细胞，并研究它们对IPF成纤维细胞以及博来霉素损伤大鼠的旁分泌作用。基底样细胞主要定位于IPF外周肺组织中的病理性细支气管化生区域或蜂窝状囊肿。单细胞RNA测序（scRNA-seq）显示出总体同质性、基底细胞标志物细胞角蛋白KRT5和KRT17的表达，以及在大多数培养细胞中与基底细胞的转录组相似性。基底样细胞分泌大量前列腺素E2（PGE2），其条件培养基（CM）抑制IPF成纤维细胞的α平滑肌肌动蛋白（α-SMA）和胶原蛋白1A1（Col1A1），并上调基质金属蛋白酶-1（MMP-1）和肝细胞生长因子（HGF）。将CM滴注到博来霉素损伤的大鼠肺中可降低胶原蛋白含量，改善肺结构，并减少α-SMA阳性细胞。我们的数据表明，基底样细胞可能通过旁分泌机制限制IPF中异常的成纤维细胞活化和分化。
