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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Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis
Rafael Kramann,Rafael Kramann,Rebekka K. Schneider,Derek P. DiRocco,Flavia Gomes Machado,Susanne V. Fleig,Philip A. Bondzie,Joel M. Henderson,Benjamin L. Ebert,Benjamin D. Humphreys,Benjamin D. Humphreys +10 more
TL;DR: Findings implicate perivascular Gli1(+) MSC-like cells as a major cellular origin of organ fibrosis and demonstrate that these cells may be a relevant therapeutic target to prevent solid organ dysfunction after injury.
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Cellular and molecular mechanisms in kidney fibrosis
TL;DR: New findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution are focused on.
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Diverse functions of matrix metalloproteinases during fibrosis.
TL;DR: Experiments in mouse models demonstrate that MMP-dependent functions during fibrosis are not limited to effects on ECM turnover, and data from diverse models indicate that these proteinases influence cellular activities as varied as proliferation and survival, gene expression, and multiple aspects of inflammation that, in turn, impact outcomes related to fibrosis.
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TGF-β1 Signaling and Tissue Fibrosis.
TL;DR: The current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis are examined.
Journal ArticleDOI
Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis.
Ting Xie,Yizhou Wang,Nan Deng,Guanling Huang,Forough Taghavifar,Yan Geng,Ningshan Liu,Vrishika Kulur,Changfu Yao,Peter Chen,Zhengqiu Liu,Barry R. Stripp,Jie Tang,Jiurong Liang,Paul W. Noble,Dianhua Jiang +15 more
TL;DR: A collection of single-cell transcriptomes and the distinct classification of fibroblast subsets provide a new resource for understanding the fibroblasts landscape and the roles of fibrablasts in fibrotic diseases.
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.
Journal ArticleDOI
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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