A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma
Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine...
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| creator | Sivaprasad, Umasundari, PhD Askew, David J., PhD Ericksen, Mark B., BS Gibson, Aaron M., BS Stier, Matthew T Brandt, Eric B., PhD Bass, Stacey A Daines, Michael O., MD Chakir, Jamila, PhD Stringer, Keith F., MD Wert, Susan E., PhD Whitsett, Jeffrey A., MD Le Cras, Timothy D., PhD Wills-Karp, Marsha, PhD Silverman, Gary A., MD, PhD Khurana Hershey, Gurjit K., MD, PhD |
| description | Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma. Methods We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13–induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13–treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production. Conclusion Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively. |
| doi_str_mv | 10.1016/j.jaci.2010.10.009 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_856789168</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0091674910015708</els_id><sourcerecordid>3382315771</sourcerecordid><originalsourceid>FETCH-LOGICAL-c544t-4c95d74a9cdfae86a146b09beadb8370906e1239ff0bd2da25a60e184fe6f7ab3</originalsourceid><addsrcrecordid>eNqFkk2LFDEQhoMo7jj6BzxIQMRTj0k6nQ8QYVn8ggUPq15DOqlmM3YnY9It7L837cy6sAc9FXl5qlJVbyH0nJIdJVS82e_21oUdI3-EHSH6AdpQomUjFOseok1VaCMk12foSSl7Ut-t0o_RGaOUCdnJDfp-jmOKGfwSvY0zzmkEPKSMp7QUwFeQDyH2rcUh4vkaavCLm0OKOA14WtxS8CGnW61CtszXk32KHg12LPDsFLfo24f3Xy8-NZdfPn6-OL9sXMf53HCnOy-51c4PFpSwlIue6B6s71UriSYCKGv1MJDeM29ZZwUBqvgAYpC2b7fo9bFubeLnAmU2UygOxtFGqAMY1QmpNBXq_yRjmjBORCVf3iP3acmxjmFox6ViSglWKXakXE6lZBjMIYfJ5htDiVntMXuz2mNWe1ZtXf4WvTiVXvoJ_N-UWz8q8OoE2OLsOGQbXSh3XKsY7-jKvT1yUJf7K0A2xQWIDnzI4GbjU_h3H-_upbsxxFB__AE3UO7mNYUZYq7WQ1rviBJCO0lU-xuUlMHn</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1547828862</pqid></control><display><type>article</type><title>A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Sivaprasad, Umasundari, PhD ; Askew, David J., PhD ; Ericksen, Mark B., BS ; Gibson, Aaron M., BS ; Stier, Matthew T ; Brandt, Eric B., PhD ; Bass, Stacey A ; Daines, Michael O., MD ; Chakir, Jamila, PhD ; Stringer, Keith F., MD ; Wert, Susan E., PhD ; Whitsett, Jeffrey A., MD ; Le Cras, Timothy D., PhD ; Wills-Karp, Marsha, PhD ; Silverman, Gary A., MD, PhD ; Khurana Hershey, Gurjit K., MD, PhD</creator><creatorcontrib>Sivaprasad, Umasundari, PhD ; Askew, David J., PhD ; Ericksen, Mark B., BS ; Gibson, Aaron M., BS ; Stier, Matthew T ; Brandt, Eric B., PhD ; Bass, Stacey A ; Daines, Michael O., MD ; Chakir, Jamila, PhD ; Stringer, Keith F., MD ; Wert, Susan E., PhD ; Whitsett, Jeffrey A., MD ; Le Cras, Timothy D., PhD ; Wills-Karp, Marsha, PhD ; Silverman, Gary A., MD, PhD ; Khurana Hershey, Gurjit K., MD, PhD</creatorcontrib><description>Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma. Methods We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13–induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13–treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production. Conclusion Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2010.10.009</identifier><identifier>PMID: 21126757</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Allergy and Immunology ; Animals ; Asthma ; Asthma - immunology ; Asthma - metabolism ; Asthma - pathology ; Avian erythroblastosis virus ; Biological and medical sciences ; Bronchoalveolar Lavage Fluid ; Cell adhesion & migration ; Cell Separation ; Chronic obstructive pulmonary disease, asthma ; Dermatophagoides pteronyssinus ; Dust ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Gene Expression ; Gene Expression Regulation - immunology ; Goblet cells ; Goblet Cells - immunology ; Goblet Cells - metabolism ; hyperplasia ; IL-13 ; Immunoglobulin E - blood ; Immunoglobulin G - blood ; Immunohistochemistry ; Immunopathology ; Kinases ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mucus - immunology ; Mucus - secretion ; Pneumology ; Proto-Oncogene Proteins c-ets - biosynthesis ; Proto-Oncogene Proteins c-ets - immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Serpins - immunology ; Serpins - metabolism ; SPDEF ; Transcription factors</subject><ispartof>Journal of allergy and clinical immunology, 2011-01, Vol.127 (1), p.254-261.e6</ispartof><rights>American Academy of Allergy, Asthma & Immunology</rights><rights>2010 American Academy of Allergy, Asthma & Immunology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c544t-4c95d74a9cdfae86a146b09beadb8370906e1239ff0bd2da25a60e184fe6f7ab3</citedby><cites>FETCH-LOGICAL-c544t-4c95d74a9cdfae86a146b09beadb8370906e1239ff0bd2da25a60e184fe6f7ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaci.2010.10.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23824517$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21126757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sivaprasad, Umasundari, PhD</creatorcontrib><creatorcontrib>Askew, David J., PhD</creatorcontrib><creatorcontrib>Ericksen, Mark B., BS</creatorcontrib><creatorcontrib>Gibson, Aaron M., BS</creatorcontrib><creatorcontrib>Stier, Matthew T</creatorcontrib><creatorcontrib>Brandt, Eric B., PhD</creatorcontrib><creatorcontrib>Bass, Stacey A</creatorcontrib><creatorcontrib>Daines, Michael O., MD</creatorcontrib><creatorcontrib>Chakir, Jamila, PhD</creatorcontrib><creatorcontrib>Stringer, Keith F., MD</creatorcontrib><creatorcontrib>Wert, Susan E., PhD</creatorcontrib><creatorcontrib>Whitsett, Jeffrey A., MD</creatorcontrib><creatorcontrib>Le Cras, Timothy D., PhD</creatorcontrib><creatorcontrib>Wills-Karp, Marsha, PhD</creatorcontrib><creatorcontrib>Silverman, Gary A., MD, PhD</creatorcontrib><creatorcontrib>Khurana Hershey, Gurjit K., MD, PhD</creatorcontrib><title>A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma. Methods We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13–induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13–treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production. Conclusion Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - immunology</subject><subject>Asthma - metabolism</subject><subject>Asthma - pathology</subject><subject>Avian erythroblastosis virus</subject><subject>Biological and medical sciences</subject><subject>Bronchoalveolar Lavage Fluid</subject><subject>Cell adhesion & migration</subject><subject>Cell Separation</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Dermatophagoides pteronyssinus</subject><subject>Dust</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation - immunology</subject><subject>Goblet cells</subject><subject>Goblet Cells - immunology</subject><subject>Goblet Cells - metabolism</subject><subject>hyperplasia</subject><subject>IL-13</subject><subject>Immunoglobulin E - blood</subject><subject>Immunoglobulin G - blood</subject><subject>Immunohistochemistry</subject><subject>Immunopathology</subject><subject>Kinases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Mucus - immunology</subject><subject>Mucus - secretion</subject><subject>Pneumology</subject><subject>Proto-Oncogene Proteins c-ets - biosynthesis</subject><subject>Proto-Oncogene Proteins c-ets - immunology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Serpins - immunology</subject><subject>Serpins - metabolism</subject><subject>SPDEF</subject><subject>Transcription factors</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2LFDEQhoMo7jj6BzxIQMRTj0k6nQ8QYVn8ggUPq15DOqlmM3YnY9It7L837cy6sAc9FXl5qlJVbyH0nJIdJVS82e_21oUdI3-EHSH6AdpQomUjFOseok1VaCMk12foSSl7Ut-t0o_RGaOUCdnJDfp-jmOKGfwSvY0zzmkEPKSMp7QUwFeQDyH2rcUh4vkaavCLm0OKOA14WtxS8CGnW61CtszXk32KHg12LPDsFLfo24f3Xy8-NZdfPn6-OL9sXMf53HCnOy-51c4PFpSwlIue6B6s71UriSYCKGv1MJDeM29ZZwUBqvgAYpC2b7fo9bFubeLnAmU2UygOxtFGqAMY1QmpNBXq_yRjmjBORCVf3iP3acmxjmFox6ViSglWKXakXE6lZBjMIYfJ5htDiVntMXuz2mNWe1ZtXf4WvTiVXvoJ_N-UWz8q8OoE2OLsOGQbXSh3XKsY7-jKvT1yUJf7K0A2xQWIDnzI4GbjU_h3H-_upbsxxFB__AE3UO7mNYUZYq7WQ1rviBJCO0lU-xuUlMHn</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Sivaprasad, Umasundari, PhD</creator><creator>Askew, David J., PhD</creator><creator>Ericksen, Mark B., BS</creator><creator>Gibson, Aaron M., BS</creator><creator>Stier, Matthew T</creator><creator>Brandt, Eric B., PhD</creator><creator>Bass, Stacey A</creator><creator>Daines, Michael O., MD</creator><creator>Chakir, Jamila, PhD</creator><creator>Stringer, Keith F., MD</creator><creator>Wert, Susan E., PhD</creator><creator>Whitsett, Jeffrey A., MD</creator><creator>Le Cras, Timothy D., PhD</creator><creator>Wills-Karp, Marsha, PhD</creator><creator>Silverman, Gary A., MD, PhD</creator><creator>Khurana Hershey, Gurjit K., MD, PhD</creator><general>Mosby, Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20110101</creationdate><title>A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma</title><author>Sivaprasad, Umasundari, PhD ; Askew, David J., PhD ; Ericksen, Mark B., BS ; Gibson, Aaron M., BS ; Stier, Matthew T ; Brandt, Eric B., PhD ; Bass, Stacey A ; Daines, Michael O., MD ; Chakir, Jamila, PhD ; Stringer, Keith F., MD ; Wert, Susan E., PhD ; Whitsett, Jeffrey A., MD ; Le Cras, Timothy D., PhD ; Wills-Karp, Marsha, PhD ; Silverman, Gary A., MD, PhD ; Khurana Hershey, Gurjit K., MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-4c95d74a9cdfae86a146b09beadb8370906e1239ff0bd2da25a60e184fe6f7ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - immunology</topic><topic>Asthma - metabolism</topic><topic>Asthma - pathology</topic><topic>Avian erythroblastosis virus</topic><topic>Biological and medical sciences</topic><topic>Bronchoalveolar Lavage Fluid</topic><topic>Cell adhesion & migration</topic><topic>Cell Separation</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Dermatophagoides pteronyssinus</topic><topic>Dust</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation - immunology</topic><topic>Goblet cells</topic><topic>Goblet Cells - immunology</topic><topic>Goblet Cells - metabolism</topic><topic>hyperplasia</topic><topic>IL-13</topic><topic>Immunoglobulin E - blood</topic><topic>Immunoglobulin G - blood</topic><topic>Immunohistochemistry</topic><topic>Immunopathology</topic><topic>Kinases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Mucus - immunology</topic><topic>Mucus - secretion</topic><topic>Pneumology</topic><topic>Proto-Oncogene Proteins c-ets - biosynthesis</topic><topic>Proto-Oncogene Proteins c-ets - immunology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rodents</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Serpins - immunology</topic><topic>Serpins - metabolism</topic><topic>SPDEF</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sivaprasad, Umasundari, PhD</creatorcontrib><creatorcontrib>Askew, David J., PhD</creatorcontrib><creatorcontrib>Ericksen, Mark B., BS</creatorcontrib><creatorcontrib>Gibson, Aaron M., BS</creatorcontrib><creatorcontrib>Stier, Matthew T</creatorcontrib><creatorcontrib>Brandt, Eric B., PhD</creatorcontrib><creatorcontrib>Bass, Stacey A</creatorcontrib><creatorcontrib>Daines, Michael O., MD</creatorcontrib><creatorcontrib>Chakir, Jamila, PhD</creatorcontrib><creatorcontrib>Stringer, Keith F., MD</creatorcontrib><creatorcontrib>Wert, Susan E., PhD</creatorcontrib><creatorcontrib>Whitsett, Jeffrey A., MD</creatorcontrib><creatorcontrib>Le Cras, Timothy D., PhD</creatorcontrib><creatorcontrib>Wills-Karp, Marsha, PhD</creatorcontrib><creatorcontrib>Silverman, Gary A., MD, PhD</creatorcontrib><creatorcontrib>Khurana Hershey, Gurjit K., MD, PhD</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sivaprasad, Umasundari, PhD</au><au>Askew, David J., PhD</au><au>Ericksen, Mark B., BS</au><au>Gibson, Aaron M., BS</au><au>Stier, Matthew T</au><au>Brandt, Eric B., PhD</au><au>Bass, Stacey A</au><au>Daines, Michael O., MD</au><au>Chakir, Jamila, PhD</au><au>Stringer, Keith F., MD</au><au>Wert, Susan E., PhD</au><au>Whitsett, Jeffrey A., MD</au><au>Le Cras, Timothy D., PhD</au><au>Wills-Karp, Marsha, PhD</au><au>Silverman, Gary A., MD, PhD</au><au>Khurana Hershey, Gurjit K., MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>127</volume><issue>1</issue><spage>254</spage><epage>261.e6</epage><pages>254-261.e6</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and SERPINB4 are induced in patients with asthma; however, their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of SERPINB3 and SERPINB4, in asthma. Methods We studied wild-type Balb/c and Serpinb3a-null mice in house dust mite or IL-13–induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a-null mice compared with the wild-type mice after allergen challenge, with minimal effects on inflammation. Expression of sterile alpha motif pointed domain containing v-ets avian erythroblastosis virus E26 oncogene homolog transcription factor (SPDEF), a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13–treated Serpinb3a-null mice showed attenuated airway hyperresponsiveness, inflammation, and mucus production. Conclusion Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel nonredundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to target mucus hypersecretion effectively.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>21126757</pmid><doi>10.1016/j.jaci.2010.10.009</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Allergy and Immunology Animals Asthma Asthma - immunology Asthma - metabolism Asthma - pathology Avian erythroblastosis virus Biological and medical sciences Bronchoalveolar Lavage Fluid Cell adhesion & migration Cell Separation Chronic obstructive pulmonary disease, asthma Dermatophagoides pteronyssinus Dust Enzyme-Linked Immunosorbent Assay Flow Cytometry Fundamental and applied biological sciences. Psychology Fundamental immunology Gene Expression Gene Expression Regulation - immunology Goblet cells Goblet Cells - immunology Goblet Cells - metabolism hyperplasia IL-13 Immunoglobulin E - blood Immunoglobulin G - blood Immunohistochemistry Immunopathology Kinases Medical sciences Mice Mice, Inbred BALB C Mice, Knockout Mucus - immunology Mucus - secretion Pneumology Proto-Oncogene Proteins c-ets - biosynthesis Proto-Oncogene Proteins c-ets - immunology Reverse Transcriptase Polymerase Chain Reaction Rodents Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Serpins - immunology Serpins - metabolism SPDEF Transcription factors |
| title | A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma |
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