Phosphatidylinositol 3-kinase-dependent stabilization of alpha1(I) collagen mRNA in human lung fibroblasts
We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the expression of alpha1(I) collagen mRNA. We report that the basal level of alpha1(I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alp...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 2001-07, Vol.281 (1), p.C99-C105 |
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creator | Ricupero, D A Poliks, C F Rishikof, D C Cuttle, K A Kuang, P P Goldstein, R H |
description | We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the expression of alpha1(I) collagen mRNA. We report that the basal level of alpha1(I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alpha1(I) collagen mRNA levels after the addition of transforming growth factor-beta. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K activity decreased the stability of the alpha1(I) collagen mRNA with no change in the rate of transcription of the alpha1(I) collagen gene as assessed by Northern blotting with actinomycin D-treated fibroblasts and nuclear run-on assays. Expression of a truncated alpha1(I) collagen minigene driven by a cytomegalovirus promoter in murine fibroblasts was decreased by LY-294002 treatment. These data indicate that PI3K activation results in increased stabilization of alpha1(I) collagen mRNA. In vivo, the PI3K activity in fibroblasts may regulate basal levels of alpha1(I) collagen mRNA expression. |
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We report that the basal level of alpha1(I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alpha1(I) collagen mRNA levels after the addition of transforming growth factor-beta. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K activity decreased the stability of the alpha1(I) collagen mRNA with no change in the rate of transcription of the alpha1(I) collagen gene as assessed by Northern blotting with actinomycin D-treated fibroblasts and nuclear run-on assays. Expression of a truncated alpha1(I) collagen minigene driven by a cytomegalovirus promoter in murine fibroblasts was decreased by LY-294002 treatment. These data indicate that PI3K activation results in increased stabilization of alpha1(I) collagen mRNA. In vivo, the PI3K activity in fibroblasts may regulate basal levels of alpha1(I) collagen mRNA expression.</description><identifier>ISSN: 0363-6143</identifier><identifier>PMID: 11401831</identifier><language>eng</language><publisher>United States</publisher><subject>3T3 Cells ; Androstadienes - pharmacology ; Animals ; Blotting, Northern ; Cells, Cultured ; Chromones - pharmacology ; Collagen - genetics ; Collagen - metabolism ; Cycloheximide - pharmacology ; Dactinomycin - pharmacology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - pharmacology ; Fibroblasts - metabolism ; Gene Expression Regulation ; Humans ; Immunoblotting ; Kinetics ; Lung - cytology ; Mice ; Morpholines - pharmacology ; Nucleic Acid Synthesis Inhibitors - pharmacology ; Phosphatidylinositol 3-Kinases - antagonists & inhibitors ; Phosphatidylinositol 3-Kinases - metabolism ; Protein Synthesis Inhibitors - pharmacology ; Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; RNA Stability - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transfection</subject><ispartof>American Journal of Physiology: Cell Physiology, 2001-07, Vol.281 (1), p.C99-C105</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11401831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ricupero, D A</creatorcontrib><creatorcontrib>Poliks, C F</creatorcontrib><creatorcontrib>Rishikof, D C</creatorcontrib><creatorcontrib>Cuttle, K A</creatorcontrib><creatorcontrib>Kuang, P P</creatorcontrib><creatorcontrib>Goldstein, R H</creatorcontrib><title>Phosphatidylinositol 3-kinase-dependent stabilization of alpha1(I) collagen mRNA in human lung fibroblasts</title><title>American Journal of Physiology: Cell Physiology</title><addtitle>Am J Physiol Cell Physiol</addtitle><description>We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the expression of alpha1(I) collagen mRNA. We report that the basal level of alpha1(I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alpha1(I) collagen mRNA levels after the addition of transforming growth factor-beta. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K activity decreased the stability of the alpha1(I) collagen mRNA with no change in the rate of transcription of the alpha1(I) collagen gene as assessed by Northern blotting with actinomycin D-treated fibroblasts and nuclear run-on assays. Expression of a truncated alpha1(I) collagen minigene driven by a cytomegalovirus promoter in murine fibroblasts was decreased by LY-294002 treatment. These data indicate that PI3K activation results in increased stabilization of alpha1(I) collagen mRNA. In vivo, the PI3K activity in fibroblasts may regulate basal levels of alpha1(I) collagen mRNA expression.</description><subject>3T3 Cells</subject><subject>Androstadienes - pharmacology</subject><subject>Animals</subject><subject>Blotting, Northern</subject><subject>Cells, Cultured</subject><subject>Chromones - pharmacology</subject><subject>Collagen - genetics</subject><subject>Collagen - metabolism</subject><subject>Cycloheximide - pharmacology</subject><subject>Dactinomycin - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Kinetics</subject><subject>Lung - cytology</subject><subject>Mice</subject><subject>Morpholines - pharmacology</subject><subject>Nucleic Acid Synthesis Inhibitors - pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Protein Synthesis Inhibitors - pharmacology</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>RNA Stability - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Transfection</subject><issn>0363-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kL1OwzAYRT2AaCm8AvKEYIjkz3adeKwqfipVgFD3yI7t1sWxQ5wM5emJRJnucu7R1b1Ac8IEKwRwNkPXOR8JIZwKeYVmAJxAxWCOjh-HlLuDGrw5BR9T9kMKmBVfPqpsC2M7G42NA86D0j74n4lMESeHVZhq8LB5xE0KQe1txO3n2wr7iA9jqyIOY9xj53WfdFB5yDfo0qmQ7e05F2j3_LRbvxbb95fNerUtuiWHAoRlzEFJK6i405XQsiRVqRk3vFEOpOQGnHSKARWUNk3jbEnoEgwvKwuCLdD9n7br0_do81C3Pjd2mhhtGnNdEkkZI3IC787gqFtr6q73repP9f857BcGBF_p</recordid><startdate>200107</startdate><enddate>200107</enddate><creator>Ricupero, D A</creator><creator>Poliks, C F</creator><creator>Rishikof, D C</creator><creator>Cuttle, K A</creator><creator>Kuang, P P</creator><creator>Goldstein, R H</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200107</creationdate><title>Phosphatidylinositol 3-kinase-dependent stabilization of alpha1(I) collagen mRNA in human lung fibroblasts</title><author>Ricupero, D A ; Poliks, C F ; Rishikof, D C ; Cuttle, K A ; Kuang, P P ; Goldstein, R H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p541-16e33f1728184fb86b97087b34d4caf1994d1f9fa312622cccfe70251d478e163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>3T3 Cells</topic><topic>Androstadienes - pharmacology</topic><topic>Animals</topic><topic>Blotting, Northern</topic><topic>Cells, Cultured</topic><topic>Chromones - pharmacology</topic><topic>Collagen - genetics</topic><topic>Collagen - metabolism</topic><topic>Cycloheximide - pharmacology</topic><topic>Dactinomycin - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Kinetics</topic><topic>Lung - cytology</topic><topic>Mice</topic><topic>Morpholines - pharmacology</topic><topic>Nucleic Acid Synthesis Inhibitors - pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - antagonists & inhibitors</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Protein Synthesis Inhibitors - pharmacology</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>RNA Stability - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ricupero, D A</creatorcontrib><creatorcontrib>Poliks, C F</creatorcontrib><creatorcontrib>Rishikof, D C</creatorcontrib><creatorcontrib>Cuttle, K A</creatorcontrib><creatorcontrib>Kuang, P P</creatorcontrib><creatorcontrib>Goldstein, R H</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>American Journal of Physiology: Cell Physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ricupero, D A</au><au>Poliks, C F</au><au>Rishikof, D C</au><au>Cuttle, K A</au><au>Kuang, P P</au><au>Goldstein, R H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphatidylinositol 3-kinase-dependent stabilization of alpha1(I) collagen mRNA in human lung fibroblasts</atitle><jtitle>American Journal of Physiology: Cell Physiology</jtitle><addtitle>Am J Physiol Cell Physiol</addtitle><date>2001-07</date><risdate>2001</risdate><volume>281</volume><issue>1</issue><spage>C99</spage><epage>C105</epage><pages>C99-C105</pages><issn>0363-6143</issn><abstract>We investigated the role of phosphatidylinositol 3-kinase (PI3K) in the expression of alpha1(I) collagen mRNA. We report that the basal level of alpha1(I) collagen mRNA was reduced when PI3K activity was inhibited by either LY-294002 or wortmannin. These PI3K inhibitors also blocked increases of alpha1(I) collagen mRNA levels after the addition of transforming growth factor-beta. The effect of PI3K inhibition was abolished by the removal of the inhibitor or by the addition of cycloheximide. Inhibition of PI3K activity decreased the stability of the alpha1(I) collagen mRNA with no change in the rate of transcription of the alpha1(I) collagen gene as assessed by Northern blotting with actinomycin D-treated fibroblasts and nuclear run-on assays. Expression of a truncated alpha1(I) collagen minigene driven by a cytomegalovirus promoter in murine fibroblasts was decreased by LY-294002 treatment. These data indicate that PI3K activation results in increased stabilization of alpha1(I) collagen mRNA. In vivo, the PI3K activity in fibroblasts may regulate basal levels of alpha1(I) collagen mRNA expression.</abstract><cop>United States</cop><pmid>11401831</pmid></addata></record> |
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subjects | 3T3 Cells Androstadienes - pharmacology Animals Blotting, Northern Cells, Cultured Chromones - pharmacology Collagen - genetics Collagen - metabolism Cycloheximide - pharmacology Dactinomycin - pharmacology Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Fibroblasts - metabolism Gene Expression Regulation Humans Immunoblotting Kinetics Lung - cytology Mice Morpholines - pharmacology Nucleic Acid Synthesis Inhibitors - pharmacology Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Protein Synthesis Inhibitors - pharmacology Protein-Serine-Threonine Kinases Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt RNA Stability - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Transfection |
title | Phosphatidylinositol 3-kinase-dependent stabilization of alpha1(I) collagen mRNA in human lung fibroblasts |
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