{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:05:30Z","timestamp":1789362330880,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>High-altitude pulmonary edema (HAPE) is a severe complication of rapid exposure to high-altitude hypoxia, but its molecular mechanisms remain incompletely understood. This study aimed to characterize lung proteomic alterations in HAPE and identify candidate proteins associated with its pathophysiological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Wistar rats were randomly allocated to control and HAPE model groups (n = 20\/group). The HAPE model was induced by exposure to simulated altitude (7,000 m) under hypobaric hypoxia combined with treadmill exercise for 48\u00a0h. Pulmonary edema was evaluated by lung wet-to-dry (W\/D) weight ratio, bronchoalveolar lavage fluid (BALF) protein concentration, inflammatory cytokine measurement, and histopathological examination. Lung proteomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS\/MS), followed by GO, KEGG, and PPI network analyses. Candidate proteins were further validated using Western blotting, immunohistochemistry, and RT-qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HAPE rats exhibited prominent pulmonary edema characterized by increased lung W\/D ratios, elevated BALF protein leakage, enhanced production of inflammatory cytokines, and marked interstitial edema. Proteomic analysis identified 5,250 proteins, among which 288 DEPs were detected, including 160 upregulated and 128 downregulated proteins. Functional enrichment analysis revealed that these DEPs were primarily associated with immune and inflammatory responses, extracellular matrix organization, glycerophospholipid metabolism, phosphatidylinositol signaling, and cell adhesion pathways. Multi-level validation confirmed increased expression of MMP9, MMP8, Serpine1 (PAI-1), MPO, HK3, and MAP3K6 at both protein and transcriptional levels. PPI network analysis indicated that MMP9 represented a central hub protein with the highest interaction connectivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a comprehensive proteomic profile of HAPE lung tissue and highlights the involvement of neutrophil-associated inflammation, extracellular matrix remodeling, fibrinolytic regulation, and metabolic adaptation in HAPE progression. The identified proteins, particularly MMP9, may serve as potential biomarkers and candidates for further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1894550","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:37:09Z","timestamp":1789360629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential proteomic analysis of lung tissues in rats with high-altitude pulmonary edema and screening of potential biomarkers"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongmei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1186\/s13046-021-02018-1","article-title":"Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2\/miR-181a pathway","volume":"40","author":"Dong","year":"2021","journal-title":"J. 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