{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:40:33Z","timestamp":1760236833424,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Project-ID 251293561 \u2013 SFB 1149"],"award-info":[{"award-number":["Project-ID 251293561 \u2013 SFB 1149"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We previously showed that attenuated lung injury after hemorrhagic shock (HS) coincided with enhanced levels of the glucocorticoid (GC) receptor (GR) in lung tissue of swine. Here, we investigated the effects of impaired GR signaling on the lung during resuscitated HS using a dysfunctional GR mouse model (GRdim\/dim). In a mouse intensive care unit, HS led to impaired lung mechanics and aggravated lung inflammation in GRdim\/dim mice compared to wildtype mice (GR+\/+). After HS, high levels of the pro-inflammatory and pro-apoptotic transcription factor STAT1\/pSTAT1 were found in lung samples from GRdim\/dim mice. Lungs of GRdim\/dim mice revealed apoptosis, most likely as consequence of reduced expression of the lung-protective Angpt1 compared to GR+\/+ after HS. RNA-sequencing revealed increased expression of pro-apoptotic and cytokine-signaling associated genes in lung tissue of GRdim\/dim mice. Furthermore, high levels of pro-inflammatory cytokines and iNOS were found in lungs of GRdim\/dim mice. Our results indicate impaired repression of STAT1\/pSTAT1 due to dysfunctional GR signaling in GRdim\/dim mice, which leads to increased inflammation and apoptosis in the lungs. These data highlight the crucial role of functional GR signaling to attenuate HS-induced lung damage.<\/jats:p>","DOI":"10.3390\/cells11010112","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T21:41:21Z","timestamp":1640900481000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired Glucocorticoid Receptor Signaling Aggravates Lung Injury after Hemorrhagic Shock"],"prefix":"10.3390","volume":"11","author":[{"given":"Jonathan M.","family":"Preuss","sequence":"first","affiliation":[{"name":"Institute of Comparative Molecular Endocrinology (CME), Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Burret","sequence":"additional","affiliation":[{"name":"Institute of Comparative Molecular Endocrinology (CME), Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gr\u00f6ger","sequence":"additional","affiliation":[{"name":"Institute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Kress","sequence":"additional","affiliation":[{"name":"Institute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Scheuerle","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan P.","family":"Tuckermann","sequence":"additional","affiliation":[{"name":"Institute of Comparative Molecular Endocrinology (CME), Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wepler","sequence":"additional","affiliation":[{"name":"Institute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, 89081 Ulm, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-9488","authenticated-orcid":false,"given":"Sabine","family":"Vettorazzi","sequence":"additional","affiliation":[{"name":"Institute of Comparative Molecular Endocrinology (CME), Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.3389\/fimmu.2019.01859","article-title":"Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor","volume":"10","author":"Caratti","year":"2019","journal-title":"Front. 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