{"id":23189,"date":"2023-01-04T04:59:00","date_gmt":"2023-01-03T20:59:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=23189"},"modified":"2023-01-04T13:17:04","modified_gmt":"2023-01-04T05:17:04","slug":"blue-journal%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e6%96%b0%e5%86%a0%e8%82%ba%e7%82%8e%e7%b2%98%e6%b6%b2%e8%93%84%e7%a7%af%e7%9a%84%e5%8f%91%e7%94%9f%e7%8e%87%e4%b8%8e%e6%9c%ba%e5%88%b6","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=23189","title":{"rendered":"[Blue Journal\u53d1\u8868\u8bba\u6587]\uff1a\u65b0\u51a0\u80ba\u708e\u7c98\u6db2\u84c4\u79ef\u7684\u53d1\u751f\u7387\u4e0e\u673a\u5236"},"content":{"rendered":"\n<h1 class=\"wp-block-heading\">Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease<\/h1>\n\n\n\n<h3 class=\"wp-block-heading\"><a href=\"https:\/\/orcid.org\/0000-0003-2248-3376\"><\/a>Takafumi Kato,\u00a0\u00a0<a href=\"https:\/\/orcid.org\/0000-0003-3122-6937\"><\/a>Takanori Asakura,\u00a0\u00a0Caitlin E. Edwards, et al<\/h3>\n\n\n\n<h3 class=\"wp-block-heading\">Am J Respir Crit Care Med 2022 Dec 1;206(11):1336-1352.<\/h3>\n\n\n\n<h3 class=\"wp-block-heading\">doi: 10.1164\/rccm.202111-2606OC<\/h3>\n\n\n\n<h4 class=\"wp-block-heading\">Abstract<\/h4>\n\n\n\n<p><strong>Rationale:<\/strong>&nbsp;The incidence and sites of mucus accumulation and molecular regulation of mucin gene expression in coronavirus (COVID-19) lung disease have not been reported.<\/p>\n\n\n\n<p><strong>Objectives:<\/strong>&nbsp;To characterize the incidence of mucus accumulation and the mechanisms mediating mucin hypersecretion in COVID-19 lung disease.<\/p>\n\n\n\n<p><strong>Methods:<\/strong>&nbsp;Airway mucus and mucins were evaluated in COVID-19 autopsy lungs by Alcian blue and periodic acid\u2013Schiff staining, immunohistochemical staining, RNA&nbsp;<em>in situ<\/em>&nbsp;hybridization, and spatial transcriptional profiling. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected human bronchial epithelial (HBE) cultures were used to investigate mechanisms of SARS-CoV-2\u2013induced mucin expression and synthesis and test candidate countermeasures.<\/p>\n\n\n\n<p><strong>Measurements and Main Results:<\/strong>&nbsp;MUC5B and variably MUC5AC RNA concentrations were increased throughout all airway regions of COVID-19 autopsy lungs, notably in the subacute\/chronic disease phase after SARS-CoV-2 clearance. In the distal lung, MUC5B-dominated mucus plugging was observed in 90% of subjects with COVID-19 in both morphologically identified bronchioles and microcysts, and MUC5B accumulated in damaged alveolar spaces. SARS-CoV-2\u2013infected HBE cultures exhibited peak titers 3 days after inoculation, whereas induction of MUC5B\/MUC5AC peaked 7\u201314 days after inoculation. SARS-CoV-2 infection of HBE cultures induced expression of epidermal growth factor receptor (EGFR) ligands and inflammatory cytokines (e.g., IL-1\u03b1\/\u03b2) associated with mucin gene regulation. Inhibiting EGFR\/IL-1R pathways or administration of dexamethasone reduced SARS-CoV-2\u2013induced mucin expression.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf1.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf2.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf3.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf4.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf5.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf6.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf7.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf8.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/www.atsjournals.org\/na101\/home\/literatum\/publisher\/thoracic\/journals\/content\/ajrccm\/2022\/ajrccm.2022.206.issue-11\/rccm.202111-2606oc\/20221116\/images\/large\/rccm.202111-2606ocf9.jpeg\" alt=\"\"\/><\/figure>\n\n\n\n<p><strong>Conclusions:<\/strong>&nbsp;SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation after SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease.<strong>Keywords<\/strong>:&nbsp;&nbsp;<a href=\"https:\/\/www.atsjournals.org\/keyword\/COVID-19\">COVID-19<\/a>;&nbsp;&nbsp;<a href=\"https:\/\/www.atsjournals.org\/keyword\/Sars-cov-2\">SARS-CoV-2<\/a>;&nbsp;&nbsp;<a href=\"https:\/\/www.atsjournals.org\/keyword\/Airway+Mucin\">airway mucin<\/a>;&nbsp;&nbsp;<a href=\"https:\/\/www.atsjournals.org\/keyword\/MUC5B\">MUC5B<\/a>;&nbsp;&nbsp;<a href=\"https:\/\/www.atsjournals.org\/keyword\/MUC5AC\">MUC5AC<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Prevalence and Mechanisms of Mucus Accumulation in COVI [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23189"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=23189"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23189\/revisions"}],"predecessor-version":[{"id":23190,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23189\/revisions\/23190"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=23189"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=23189"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=23189"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}