{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:18:21Z","timestamp":1788434301901,"version":"build-2803163510"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Severe burn injury triggers profound skeletal muscle atrophy through incompletely understood molecular mechanisms. This study investigated the role of protein kinase C (PKC) isoforms in burn-induced muscle wasting and evaluated potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined PKC isoform expression in skeletal muscle biopsies from burn patients with second-degree (n = 5) and third-degree burns (n = 5) at 7\u00a0days post-injury. Mouse burn models were established to investigate PKC signaling at 14\u00a0days post-injury. Muscle-specific PKC-lambda (PKC-\u03bb) knockout mice and pharmacological inhibition with [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1) were employed. C2C12 myotubes were used for mechanistic studies with signal transducer and activator of transcription 3 (STAT3) overexpression experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among six PKC isoforms examined, only PKC-\u03bb was selectively upregulated in third-degree versus second-degree burns in both humans and mice. Third-degree burns caused 39.5% muscle mass loss and 57.3% grip strength reduction, accompanied by PKC-\u03bb activation and downstream STAT3-CCAAT\/enhancer-binding protein delta (C\/EBP\u03b4)\/myostatin catabolic signaling. Muscle-specific PKC-\u03bb knockout mice showed significant protection against burn-induced muscle atrophy.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies demonstrated that PKC-\u03bb regulates muscle catabolism through STAT3 activation, as STAT3 overexpression reversed protective effects of PKC-\u03bb inhibition. Pharmacological PKC-\u03bb inhibition with ICA-1 restored muscle mass to 85.5% and grip strength to 73.6% of control levels while suppressing the PKC-\u03bb\/STAT3-C\/EBP\u03b4 catabolic cascade.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PKC-\u03bb serves as a critical upstream mediator linking severe burn injury to skeletal muscle atrophy through STAT3-C\/EBP\u03b4 catabolic signaling. These findings establish PKC-\u03bb as a promising therapeutic target for preventing burn-induced muscle wasting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1839235","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:44:13Z","timestamp":1788432253000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein kinase C-\u03bb drives third-degree burn-induced muscle wasting via STAT3-dependent catabolic pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Peilong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Burn and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/0959-440x(95)80103-0","article-title":"The protein kinase C and protein kinase C related gene families","volume":"5","author":"Dekker","year":"1995","journal-title":"Curr. 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