Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury.

Animals Cicatrix / genetics Collagen Type I / genetics Collagen Type I, alpha 1 Chain Collagen Type III / genetics Collagen Type V / deficiency Extracellular Matrix / genetics Female Fibrosis / genetics Gene Expression Regulation / genetics Heart Injuries / metabolism Integrins / antagonists & inhibitors Isoproterenol / pharmacology Male Mechanotransduction, Cellular / genetics Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Atomic Force / instrumentation Microscopy, Electron, Transmission Myocardial Contraction / drug effects Myofibroblasts / cytology Principal Component Analysis Proteomics RNA-Seq Single-Cell Analysis
Col5a1 cilengitide collagen V fibrosis heart scar integrins scar mechanics

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
06 08 2020
Historique:
received: 15 11 2019
revised: 17 03 2020
accepted: 18 06 2020
pubmed: 6 7 2020
medline: 30 3 2021
entrez: 5 7 2020
Statut: ppublish

Résumé

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.

Identifiants

DOI: 10.1016/j.cell.2020.06.030 PMID: 32621799 PMC: PMC7415659
pubmed: 32621799
pii: S0092-8674(20)30807-2
doi: 10.1016/j.cell.2020.06.030
pmc: PMC7415659
mid: NIHMS1607837
pii:
doi:

Substances chimiques

COL3A1 protein, mouse 0
Collagen Type I 0
Collagen Type I, alpha 1 Chain 0
Collagen Type III 0
Collagen Type V 0
Integrins 0
Isoproterenol L628TT009W

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

545-562.e23

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL152176
Pays : United States
Organisme : NHLBI NIH HHS
ID : K99 HL138193
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL138193
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147883
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126204
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149658
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR048179
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137241
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL129178
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149687
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR075867
Pays : United States
Organisme : NIGMS NIH HHS
ID : K12 GM106996
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests. Based on this work, patent no: 63/002,828 “Compositions and methods for treating dysregulated wound healing” has been filed and assigned to the Regents of the University of California.

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Auteurs

Tomohiro Yokota (T)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Jackie McCourt (J)

Department of Integrative Biology and Physiology, University of California, CA 90095, USA.

Feiyang Ma (F)

Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Shuxun Ren (S)

Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Shen Li (S)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Tae-Hyung Kim (TH)

Department of Integrative Biology and Physiology, University of California, CA 90095, USA.

Yerbol Z Kurmangaliyev (YZ)

Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Rohollah Nasiri (R)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Mechanical Engineering, Sharif University of Technology, Tehran 11365-11155, Iran.

Samad Ahadian (S)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90024, USA.

Thang Nguyen (T)

Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA.

Xing Haw Marvin Tan (XHM)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095, USA.

Yonggang Zhou (Y)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Rimao Wu (R)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Abraham Rodriguez (A)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Whitaker Cohn (W)

Passarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Behaviour, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Yibin Wang (Y)

Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Julian Whitelegge (J)

Passarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Behaviour, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Sergey Ryazantsev (S)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.

Ali Khademhosseini (A)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA 90024, USA; Department of Chemical Engineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

Michael A Teitell (MA)

Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.

Pei-Yu Chiou (PY)

California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095, USA.

David E Birk (DE)

University of South Florida College of Medicine, Tampa, FL 33612, USA.

Amy C Rowat (AC)

Department of Integrative Biology and Physiology, University of California, CA 90095, USA; Department of Bioengineering, School of Engineering, University of California, Los Angeles, CA 90095, USA.

Rachelle H Crosbie (RH)

Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, CA 90095, USA.

Matteo Pellegrini (M)

Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Marcus Seldin (M)

Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, CA 92697, USA.

Aldons J Lusis (AJ)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Genetics, David Geffen School of Medicine, Los Angeles, CA 90095, USA.

Arjun Deb (A)

Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; UCLA Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA. Electronic address: adeb@mednet.ucla.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Cicatrisation de plaie › Cicatrice › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type I › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Structures macromoléculaires › Chaine alpha-1 du collagène de type I › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type III › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type V › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Matrice extracellulaire › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Plaies et blessures › Blessures du thorax › Lésions traumatiques du coeur › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Intégrines › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénols › Catéchols › Catécholamines › Isoprénaline › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mécanotransduction cellulaire › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Techniques d'investigation › Microscopie à sonde à balayage › Microscopie à force atomique › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Microscopie électronique à transmission › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Contraction musculaire › Contraction myocardique › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes du muscle lisse › Myofibroblastes › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Techniques d'investigation › Analyse en composantes principales › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › RNA-Seq › Type V Collagen in Scar Tissue Regulates the...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Analyse sur cellule unique › Type V Collagen in Scar Tissue Regulates the...