Role of lung pericytes and resident fibroblasts in the pathogenesis of pulmonary fibrosis.
Chi F. Hung,Geoffrey Linn,Yu Hua Chow,Akio Kobayashi,Kristen Mittelsteadt,William A. Altemeier,Sina A. Gharib,Lynn M. Schnapp,Jeremy S. Duffield +8 more
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TLDR
The lung contains an extensive population of Foxd1 progenitor-derived pericytes that are an important lung myofibroblast precursor population, and these studies suggest a distinct lineage of collagen-I(α)1-expressing resident fibroblasts that also expands after lung injury is a second major source of my ofibro Blasts.Abstract:
Rationale: The origin of cells that make pathologic fibrillar collagen matrix in lung disease has been controversial. Recent studies suggest mesenchymal cells may contribute directly to fibrosis.Objectives: To characterize discrete populations of mesenchymal cells in the normal mouse lung and to map their fate after bleomycin-induced lung injury.Methods: We mapped the fate of Foxd1-expressing embryonic progenitors and their progeny during lung development, adult homeostasis, and after fibrosing injury in Foxd1-Cre; Rs26-tdTomato-R mice. We studied collagen-I(α)1–producing cells in normal and diseased lungs using Coll-GFPTg mice.Measurements and Main Results: Foxd1-expressing embryonic progenitors enter lung buds before 13.5 days post-conception, expand, and form an extensive lineage of mesenchymal cells that have characteristics of pericytes. A collagen-I(α)1–expressing mesenchymal population of distinct lineage is also found in adult lung, with features of a resident fibroblast. In contrast to resident f...read more
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The elephant in the lung: Integrating lineage-tracing, molecular markers, and single cell sequencing data to identify distinct fibroblast populations during lung development and regeneration
TL;DR: Major developmental mesenchymal lineages are discussed, focusing on time of origin, major cell type, and other lineage derivatives, as well as the transgenic tools used to find and define them.
Journal ArticleDOI
Developmental mechanisms and adult stem cells for therapeutic lung regeneration.
Joo-Hyeon Lee,Emma L. Rawlins +1 more
TL;DR: The normal endogenous processes of lung development, homeostatic maintenance and repair are discussed, and the research strategies required for the development of methods for human therapeutic lung regeneration are considered.
Journal ArticleDOI
Screening for YAP Inhibitors Identifies Statins as Modulators of Fibrosis.
Daniela M. Santos,Lorena Pantano,Gina Pronzati,Paula Grasberger,Clemens K. Probst,Katharine E. Black,Jillian J Spinney,Lida P. Hariri,Royale Nichols,Yufei Lin,Michael Bieler,Peter Seither,Paul Nicklin,David Wyatt,Andrew M. Tager,Benjamin D. Medoff +15 more
TL;DR: A high-throughput small molecule screen for YAP inhibitors in primary human lung fibroblasts shows that the mevalonate pathway regulates YAP activation, and that simvastatin treatment reduces fibrosis markers in activated HLF and in the bleomycin mouse model of pulmonary fibrosis.
Journal ArticleDOI
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction
Christa F. Gaskill,Erica J. Carrier,Jonathan A. Kropski,Nathaniel C. Bloodworth,Swapna Menon,Robert F. Foronjy,Makoto Mark Taketo,Charles C. Hong,Charles C. Hong,Eric D. Austin,James West,Anna L. Means,James E. Loyd,W. David Merryman,Anna R. Hemnes,Stijn De Langhe,Timothy S. Blackwell,Dwight J. Klemm,Susan M. Majka +18 more
TL;DR: Enhanced Wnt/&bgr;-catenin signaling in ABCG2+ MPCs drives a phenotype of persistent microvascular dysfunction, abnormal angiogenesis, and subsequent exacerbation of bleomycin-induced fibrosis, which may account in part for the aberrant microvessel function and remodeling that are associated with chronic lung diseases.
Journal ArticleDOI
Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice.
Leola N. Chow,Petra Schreiner,Betina Y. Y. Ng,Bernard C. Lo,Michael R. Hughes,R. Wilder Scott,Vionarica Gusti,Samantha Lecour,Eric Simonson,Irina Manisali,Ingrid Barta,Kelly M. McNagny,Jason Crawford,Murray S. Webb,T. Michael Underhill +14 more
TL;DR: AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage, and indicates that the CxCL12-CX CR4 signaling axis is not an effective target for reducing fibrosis.
References
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Journal ArticleDOI
Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.
TL;DR: The history of investigations into pericytes, the mural cells of blood microvessels, are reviewed, emerging concepts are indicated, and problems and promise are pointed out.
Journal ArticleDOI
Endothelial/Pericyte Interactions
TL;DR: This review focuses on the advancement in recent years of the understanding of intercellular communication between endothelial and mural cells with a focus on transforming growth factor α, angiopoietins, platelet-derived growth factor, spingosine-1-phosphate, and Notch ligands and their respective receptors.
Journal ArticleDOI
The role of pericytes in blood-vessel formation and maintenance
Gabriele Bergers,Steven Song +1 more
TL;DR: This review article describes the current knowledge about the nature of pericytes and their functions during vessel growth, vessel maintenance, and pathological angiogenesis.
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Fate Tracing Reveals the Pericyte and Not Epithelial Origin of Myofibroblasts in Kidney Fibrosis
Benjamin D. Humphreys,Benjamin D. Humphreys,Shuei-Liong Lin,Shuei-Liong Lin,Akio Kobayashi,Thomas E. Hudson,Brian T. Nowlin,Joseph V. Bonventre,Joseph V. Bonventre,M. Todd Valerius,Andrew P. McMahon,Jeremy S. Duffield,Jeremy S. Duffield +12 more
TL;DR: Data indicate that therapeutic strategies directly targeting pericyte differentiation in vivo may productively impact fibrotic kidney disease.
Journal ArticleDOI
Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
TL;DR: The results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported.
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