{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:16:03Z","timestamp":1786115763994,"version":"build-2736575974"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Macrophages facilitate blastema and wound epithelium formation by clearing debris and remodeling the immune and extracellular matrix. The M1-to-M2 transition is well documented in amphibians, but its occurrence and timing in diverse lizards remain unclear. This study examined macrophage function during tail regeneration in\n                      <jats:italic>Scincella tsinlingensis<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A tail amputation model was established in\n                      <jats:italic>S. tsinlingensis<\/jats:italic>\n                      , and macrophages were depleted using clodronate liposomes (L-Clodronate). Transcriptomic analysis was performed during the wound epithelialization phase, followed by qRT-PCR and immunohistochemistry to assess immune responses, chemokine signaling, oxidative balance, myogenic regulation, and matrix metalloproteinase (MMP) activity. MMP function was further examined using GM6001 inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Macrophage depletion severely impaired tail regeneration. By 21 days post-amputation (dpa), control regenerates reached 6.1 \u00b1 2.2\u00a0mm, whereas depleted tails grew only 0.5 \u00b1 0.1\u00a0mm (P &amp;lt; 0.0001). Depletion delayed wound epithelialization and prevented blastema formation. Macrophage recruitment peaked later in depleted animals (86.8 \u00b1 13.8\u00a0at 7 dpa) than in controls (148.4 \u00b1 7.1\u00a0at 3 dpa). CTSK positive osteoclasts were reduced by \u223c47% (53 \u00b1 5.6 vs. 100.3 \u00b1 18.1, P &amp;lt; 0.05). Transcriptomic analysis identified 341 DEGs, with downregulated genes enriched in type I interferon, desmosome, and TLR\/NOD pathways.\n                      <jats:italic>TLR4<\/jats:italic>\n                      was a hub gene. qPCR and immunohistochemistry confirmed disrupted M1-to-M2 transition, suppressed cytokines (TNF\u03b1, IL-6, IL-10, TGF\u03b21), dysregulated CXCL12\/CXCR4, oxidative imbalance (gp91phox), failed myogenesis (decreased MYOD1, persistent PAX7), and reduced Ctsk, MMP2, MMP9. GM6001 matrix metalloproteinase inhibition delayed regeneration (10.2 \u00b1 1.2 vs. 1.5 \u00b1 0.1\u00a0mm at 28 dpa, P &amp;lt; 0.0001) with compensatory upregulation of MMP2\/3\/9.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Macrophages serve as central timing regulators of tail regeneration in\n                      <jats:italic>S. tsinlingensis<\/jats:italic>\n                      . Their depletion disrupts the early inflammatory switch, impairs blastema formation, and severely limits outgrowth within the 21-day observation period, whereas MMP inhibition only slows regeneration. Macrophages coordinate the immune, myogenic, and matrix remodeling programs essential for successful tissue restoration, highlighting their non-redundant role in reptile regeneration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1873713","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:33:36Z","timestamp":1785994416000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophages orchestrate tail regeneration in lizards Scincella tsinlingensis through spatiotemporal control of immunity, oxidative stress, and myogenesis"],"prefix":"10.3389","volume":"14","author":[{"given":"Qing","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongnan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanxi Normal University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/nature10390","article-title":"The genome of the green anole lizard and a comparative analysis with birds and mammals","volume":"477","author":"Alf\u00f6ldi","year":"2011","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.proghi.2013.09.001","article-title":"Histochemical, biochemical and cell biological aspects of tail regeneration in lizard, an amniote model for studies on tissue regeneration","volume":"48","author":"Alibardi","year":"2014","journal-title":"Prog. 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