Similar regulatory mechanisms of caveolins and cavins by myocardin family coactivators in arterial and bladder smooth muscle

Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN...

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Veröffentlicht in:PloS one 2017-05, Vol.12 (5), p.e0176759-e0176759
Hauptverfasser: Zhu, Baoyi, Rippe, Catarina, Thi Hien, Tran, Zeng, Jianwen, Albinsson, Sebastian, Stenkula, Karin G, Uvelius, Bengt, Swärd, Karl
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container_issue 5
container_start_page e0176759
container_title PloS one
container_volume 12
creator Zhu, Baoyi
Rippe, Catarina
Thi Hien, Tran
Zeng, Jianwen
Albinsson, Sebastian
Stenkula, Karin G
Uvelius, Bengt
Swärd, Karl
description Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. In all, these findings further support the view that myocardin family coactivators are important transcriptional drivers of caveolins and cavins in smooth muscle.
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Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. 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Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. In all, these findings further support the view that myocardin family coactivators are important transcriptional drivers of caveolins and cavins in smooth muscle.</description><subject>Acetylcholine receptors (muscarinic)</subject><subject>Actin</subject><subject>Adipocytes</subject><subject>Adipogenesis</subject><subject>Air conditioning</subject><subject>Animals</subject><subject>Aorta</subject><subject>Arteries</subject><subject>Assaying</subject><subject>Atmosphere</subject><subject>Basic Medicine</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biomechanics</subject><subject>Biosynthesis</subject><subject>Bladder</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Carbon dioxide</subject><subject>Cardiac and Cardiovascular Systems</subject><subject>Caveolins</subject><subject>Caveolins - genetics</subject><subject>Caveolins - metabolism</subject><subject>Cell and Molecular Biology</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell- och molekylärbiologi</subject><subject>Cells, Cultured</subject><subject>Cholesterol</subject><subject>Clinical Medicine</subject><subject>Coronary vessels</subject><subject>Deoxyribonucleic acid</subject><subject>Differentiation (biology)</subject><subject>Dissection</subject><subject>DNA</subject><subject>Dystrophy</subject><subject>Evolution</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genetic aspects</subject><subject>Genetic control</subject><subject>Guidelines</subject><subject>Heart diseases</subject><subject>Homeostasis</subject><subject>Hypoxia</subject><subject>Inhibition</subject><subject>Inhibitors</subject><subject>Kardiologi</subject><subject>Klinisk medicin</subject><subject>Male</subject><subject>Medical and Health Sciences</subject><subject>Medical science</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine and Health Sciences</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Movement disorders</subject><subject>Muscle, Smooth - metabolism</subject><subject>Muscles</subject><subject>Muscular dystrophy</subject><subject>Mutation</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Neurodegenerative diseases</subject><subject>Nuclear Proteins - metabolism</subject><subject>Optimization</subject><subject>Organelles</subject><subject>Parkinson's disease</subject><subject>Pharmacology</subject><subject>Physiological aspects</subject><subject>Pipes</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Promoters (Genetics)</subject><subject>Prostate cancer</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration (physiology)</subject><subject>Regulatory mechanisms (biology)</subject><subject>Rodents</subject><subject>Science</subject><subject>Smooth muscle</subject><subject>Stem cells</subject><subject>Stimulation</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription factors</subject><subject>Transcription, Genetic - genetics</subject><subject>Transcriptional Activation - genetics</subject><subject>Urinary bladder</subject><subject>Urinary Bladder - metabolism</subject><subject>Urologi och njurmedicin</subject><subject>Urology</subject><subject>Urology and Nephrology</subject><subject>Veins &amp; 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Rippe, Catarina ; Thi Hien, Tran ; Zeng, Jianwen ; Albinsson, Sebastian ; Stenkula, Karin G ; Uvelius, Bengt ; Swärd, Karl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c761t-17f4779c7636fbda6891fb95ab7d401217cdb85e5389573621c06f0ad366c8143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetylcholine receptors (muscarinic)</topic><topic>Actin</topic><topic>Adipocytes</topic><topic>Adipogenesis</topic><topic>Air conditioning</topic><topic>Animals</topic><topic>Aorta</topic><topic>Arteries</topic><topic>Assaying</topic><topic>Atmosphere</topic><topic>Basic Medicine</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Biomechanics</topic><topic>Biosynthesis</topic><topic>Bladder</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Carbon dioxide</topic><topic>Cardiac and Cardiovascular Systems</topic><topic>Caveolins</topic><topic>Caveolins - genetics</topic><topic>Caveolins - metabolism</topic><topic>Cell and Molecular Biology</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cell- och molekylärbiologi</topic><topic>Cells, Cultured</topic><topic>Cholesterol</topic><topic>Clinical Medicine</topic><topic>Coronary vessels</topic><topic>Deoxyribonucleic acid</topic><topic>Differentiation (biology)</topic><topic>Dissection</topic><topic>DNA</topic><topic>Dystrophy</topic><topic>Evolution</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genetic aspects</topic><topic>Genetic control</topic><topic>Guidelines</topic><topic>Heart diseases</topic><topic>Homeostasis</topic><topic>Hypoxia</topic><topic>Inhibition</topic><topic>Inhibitors</topic><topic>Kardiologi</topic><topic>Klinisk medicin</topic><topic>Male</topic><topic>Medical and Health Sciences</topic><topic>Medical science</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine and Health Sciences</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Movement disorders</topic><topic>Muscle, Smooth - metabolism</topic><topic>Muscles</topic><topic>Muscular dystrophy</topic><topic>Mutation</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Neurodegenerative diseases</topic><topic>Nuclear Proteins - metabolism</topic><topic>Optimization</topic><topic>Organelles</topic><topic>Parkinson's disease</topic><topic>Pharmacology</topic><topic>Physiological aspects</topic><topic>Pipes</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Promoters (Genetics)</topic><topic>Prostate cancer</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regeneration (physiology)</topic><topic>Regulatory mechanisms (biology)</topic><topic>Rodents</topic><topic>Science</topic><topic>Smooth muscle</topic><topic>Stem cells</topic><topic>Stimulation</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription factors</topic><topic>Transcription, Genetic - genetics</topic><topic>Transcriptional Activation - genetics</topic><topic>Urinary bladder</topic><topic>Urinary Bladder - metabolism</topic><topic>Urologi och njurmedicin</topic><topic>Urology</topic><topic>Urology and Nephrology</topic><topic>Veins &amp; 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Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences. Silencing of MKL1 and MKL2 in smooth muscle cells moreover reduced CAV1 and CAVIN1 mRNA levels by well over 50%, as did treatment with second generation inhibitors of MKL activity. GATA6, which modulates expression of smooth muscle-specific genes, reduced CAV1 and CAV2, whereas the cavins were unaffected or increased. Viral overexpression of MKL1 and myocardin induced caveolin and cavin expression in bladder smooth muscle cells from rats and humans and MYOCD correlated tightly with CAV1 and CAVIN1 in human bladder specimens. A recently described activator of MKL-driven transcription (ISX) failed to induce CAV1/CAVIN1 which may be due to an unusual transactivation mechanism. In all, these findings further support the view that myocardin family coactivators are important transcriptional drivers of caveolins and cavins in smooth muscle.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28542204</pmid><doi>10.1371/journal.pone.0176759</doi><tpages>e0176759</tpages><orcidid>https://orcid.org/0000-0002-7255-5510</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry
subjects Acetylcholine receptors (muscarinic)
Actin
Adipocytes
Adipogenesis
Air conditioning
Animals
Aorta
Arteries
Assaying
Atmosphere
Basic Medicine
Biochemistry
Biology and Life Sciences
Biomechanics
Biosynthesis
Bladder
Breast cancer
Cancer
Carbon dioxide
Cardiac and Cardiovascular Systems
Caveolins
Caveolins - genetics
Caveolins - metabolism
Cell and Molecular Biology
Cell culture
Cell differentiation
Cell- och molekylärbiologi
Cells, Cultured
Cholesterol
Clinical Medicine
Coronary vessels
Deoxyribonucleic acid
Differentiation (biology)
Dissection
DNA
Dystrophy
Evolution
Female
Gene expression
Gene regulation
Genetic aspects
Genetic control
Guidelines
Heart diseases
Homeostasis
Hypoxia
Inhibition
Inhibitors
Kardiologi
Klinisk medicin
Male
Medical and Health Sciences
Medical science
Medicin och hälsovetenskap
Medicine and Health Sciences
Medicinska och farmaceutiska grundvetenskaper
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metastases
Mice
Mice, Inbred C57BL
Movement disorders
Muscle, Smooth - metabolism
Muscles
Muscular dystrophy
Mutation
Myocytes, Smooth Muscle - metabolism
Neurodegenerative diseases
Nuclear Proteins - metabolism
Optimization
Organelles
Parkinson's disease
Pharmacology
Physiological aspects
Pipes
Promoter Regions, Genetic - genetics
Promoters (Genetics)
Prostate cancer
Proteins
Rats
Rats, Sprague-Dawley
Regeneration (physiology)
Regulatory mechanisms (biology)
Rodents
Science
Smooth muscle
Stem cells
Stimulation
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription factors
Transcription, Genetic - genetics
Transcriptional Activation - genetics
Urinary bladder
Urinary Bladder - metabolism
Urologi och njurmedicin
Urology
Urology and Nephrology
Veins & arteries
Wound healing
title Similar regulatory mechanisms of caveolins and cavins by myocardin family coactivators in arterial and bladder smooth muscle
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