{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:50:47Z","timestamp":1787323847283,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873934"],"award-info":[{"award-number":["81873934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic exposure to ultraviolet B (UVB) radiation induces excessive reactive oxygen species (ROS) production in dermal fibroblasts, leading to cellular senescence and skin photoaging. Ageing skin is characterised by disruption of the immune microenvironment, including impaired macrophage polarisation and reduced M2 macrophage activity. However, the contribution of M2 macrophages to fibroblast photoaging remains incompletely understood. Here, we investigated whether M2 macrophages attenuate UVB\u2010induced fibroblast senescence through ectonucleotide pyrophosphatase\/phosphodiesterase 2 (ENPP2)\u2013dependent lysophosphatidic acid (LPA)signalling. UVB\u2010induced L929 fibroblasts were treated with conditioned media derived from polarised RAW264.7 macrophages, with or without ENPP2 silencing. UVB exposure induced marked senescence, oxidative stress, and mitophagy impairment, whereas conditioned medium from M2 macrophages significantly alleviated these effects compared with M1\u2010derived conditioned medium. Notably, ENPP2 depletion in M2 macrophages substantially reduced these protective effects. M2 macrophage\u2013derived conditioned medium contained elevated LPA levels and restored UVB\u2010suppressed LPAR1 and LPAR3 expression in fibroblasts. Pharmacological inhibition of LPAR1\/3 attenuated the protective effects of M2 macrophages, while exogenous LPA supplementation restored these effects under ENPP2\u2010deficient conditions. These changes were associated with enhanced PINK1\/Parkin\u2010related mitophagy signalling and reduced oxidative stress. Collectively, these findings identify M2 macrophage\u2013derived ENPP2\/LPA signalling as a critical paracrine mechanism that mitigates UVB\u2010induced fibroblast photoaging.<\/jats:p>","DOI":"10.1111\/exd.70313","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:06:23Z","timestamp":1783055183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>M2<\/scp>\n                    Macrophage\u2013Derived\n                    <scp>ENPP2<\/scp>\n                    \/\n                    <scp>LPA<\/scp>\n                    Signalling Attenuates\n                    <scp>UVB<\/scp>\n                    \u2010Induced Fibroblast Photoaging via\n                    <scp>LPAR1<\/scp>\n                    \/3"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6540-801X","authenticated-orcid":false,"given":"Meiqi","family":"Lu","sequence":"first","affiliation":[{"name":"The Second Clinical College of Shandong University  Jinan Shandong China"},{"name":"Department of Plastic and Burns Surgery The Second Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Department of Emergency The Second Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Clinical College of Shandong University  Jinan Shandong China"},{"name":"Department of Plastic and Burns Surgery The Second Qilu Hospital of Shandong University  Jinan Shandong China"},{"name":"Department of Emergency The Second Qilu Hospital of Shandong University  Jinan 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