{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:02:11Z","timestamp":1790499731224,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1I1A1A01059951"],"award-info":[{"award-number":["NRF-2019R1I1A1A01059951"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health and Welfare, Republic of Korea","doi-asserted-by":"publisher","award":["SMX122081"],"award-info":[{"award-number":["SMX122081"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea Ministry of Science, Ministry of Education","doi-asserted-by":"publisher","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea Ministry of Science, Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2019R1I1A1A01059951"],"award-info":[{"award-number":["NRF-2019R1I1A1A01059951"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korea Ministry of Science, Ministry of Education","doi-asserted-by":"publisher","award":["SMX122081"],"award-info":[{"award-number":["SMX122081"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Samsung Medical Center","award":["HI14C3484"],"award-info":[{"award-number":["HI14C3484"]}]},{"name":"Samsung Medical Center","award":["NRF-2019R1I1A1A01059951"],"award-info":[{"award-number":["NRF-2019R1I1A1A01059951"]}]},{"name":"Samsung Medical Center","award":["SMX122081"],"award-info":[{"award-number":["SMX122081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Formyl peptide receptor (FPR) 2 is known to play a critical role in regulating inflammation, including either the pro-inflammatory or pro-resolving effects. However, its role in neonatal hyperoxia-induced lung injury has not been delineated. In this study, we investigate whether mesenchymal stem cells (MSCs) attenuate hyperoxia-induced neonatal lung injury by regulating FPR2 activity. We observed a significant increase in FPR2 levels in alveolar macrophages (RAW264.7 cells) after H2O2-induced stress, which decreased after MSC treatment. In the H2O2-induction model, increased levels of inflammatory cytokines (IL-1\u03b1 and TNF-\u03b1) were significantly reduced in RAW264.7 cells after treatment with WRW4, an inhibitor of FPR2, or MSCs. Viability of lung epithelial cells and endothelial cells was significantly improved when cultured in the conditioned media of RAW264.7 cells treated with WRW4 or MSCs, compared to when cultured in the conditioned media of control RAW265.7 cells exposed to H2O2. For the in vivo study, wild-type and FPR2 knockout (FPR2\u2212\/\u2212) C57\/BL6 mouse pups were randomly exposed to 80% oxygen or room air from postnatal day (P) 1 to P14. At P5, 2 \u00d7 105 MSCs were transplanted intratracheally. MSCs reduced the elevated FPR2 activity at P7 and improved the decreased FPR2 activity as well as the increased immuno-stained FPR2 activity in alveolar macrophages in hyperoxic lungs at P14. Both FPR2\u2212\/\u2212 and MSCs similarly attenuated impaired alveolarization and angiogenesis, and increased apoptosis and inflammation of hyperoxic lungs without synergistic effects. Our findings suggest that the protective effects of MSCs in hyperoxic lung injury might be related to indirect modulation of FPR2 activity, at least of alveolar macrophages in neonatal mice.<\/jats:p>","DOI":"10.3390\/ijms231810604","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Young Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Samsung Medical Center, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Yoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kyung","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-2938","authenticated-orcid":false,"given":"Yun Sil","family":"Chang","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Soon","family":"Park","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy Institute, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Samsung Medical Center, Seoul 06351, Korea"},{"name":"Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3727\/096368911X565038a","article-title":"Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats","volume":"20","author":"Chang","year":"2011","journal-title":"Cell Transpl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kim, Y.E., Park, W.S., Ahn, S.Y., Sung, D.K., and Chang, Y.S. 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