{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:48:38Z","timestamp":1791838118609,"version":"4.3.4"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272294"],"award-info":[{"award-number":["82272294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010909","name":"MOST | NSFC | Excellent Young Scientists Fund","doi-asserted-by":"publisher","award":["no number"],"award-info":[{"award-number":["no number"]}],"id":[{"id":"10.13039\/501100010909","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Fibroblasts are heterogeneous stromal cells with remarkable lineage plasticity, generating distinct subsets that orchestrate either regenerative repair or fibrotic remodeling. However, how the pro-fibrotic fibroblast state is molecularly stabilized after activation remains poorly defined. Here, we identify the long noncoding RNA\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    as an essential regulator of fibroblast fate maintenance and fibrogenic activity.\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    is markedly enriched in CD90+ fibroblasts within human hypertrophic scars and keloids. Genetic deletion of\n                    <jats:italic toggle=\"yes\">Snhg26<\/jats:italic>\n                    in fibroblasts or antisense oligonucleotide\u2013mediated silencing disrupts mesenchymal identity, suppresses extracellular matrix synthesis, and dramatically attenuates scar formation in murine and xenograft models. Single-cell transcriptomics reveal that loss of\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    promotes a mesenchymal-to-papillary fibroblast transition, indicating that\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    enforces lineage stability within the scar-forming fibroblast pool. Mechanistically,\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    functions as a nuclear scaffold that binds the RNA-binding protein PTBP1, enabling PTBP1-directed alternative polyadenylation of\n                    <jats:italic toggle=\"yes\">AKT3<\/jats:italic>\n                    . This interaction favors distal polyadenylation site usage, generating a long 3\u2032UTR\n                    <jats:italic toggle=\"yes\">AKT3<\/jats:italic>\n                    isoform with enhanced stability, thereby sustaining AKT3 expression and downstream pro-fibrotic signaling. Upstream, TNF\u03b1\u2013ERK\u2013STAT3 signaling induces\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    transcription, linking chronic inflammation to persistent posttranscriptional activation of fibrogenic pathways. Collectively, these findings define a lncRNA-based regulatory checkpoint in which the\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    \u2013PTBP1\u2013AKT3 axis stabilizes mesenchymal fibroblast identity and drives extracellular matrix accumulation. Targeting\n                    <jats:italic toggle=\"yes\">SNHG26<\/jats:italic>\n                    offers a promising therapeutic strategy for preventing pathological scar formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2601536123","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:06:56Z","timestamp":1787850416000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>SNHG26<\/i>\n                    orchestrates pro-fibrotic fibroblast maintenance via PTBP1-mediated alternative polyadenylation of\n                    <i>AKT3<\/i>\n                    in dermal fibrosis"],"prefix":"10.1073","volume":"123","author":[{"given":"Ling","family":"Pan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02drdmm93","id-type":"ROR","asserted-by":"publisher"}],"name":"Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & 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Kishor , Activation and inhibition of nonsense-mediated mRNA decay control the abundance of alternative polyadenylation products. 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Li The RNA-sequencing data of SNHG26-knockdown fibroblasts. Genome Sequence Archive for Human (GSA-Human). https:\/\/ngdc.cncb.ac.cn\/gsa-human\/browse\/HRA018399. Deposited 9 May 2026."},{"key":"e_1_3_5_51_2","author":"Li D.","unstructured":"D. Li, Full-length transcriptome analysis of keloid fibroblasts with SNHG26 or PTBP1 knockdown. Genome Sequence Archive for Human (GSA-Human). https:\/\/ngdc.cncb.ac.cn\/gsa-human\/browse\/HRA018418. Deposited 10 May 2026.","journal-title":"Genome"},{"key":"e_1_3_5_52_2","unstructured":"D. Li CUTTag-based profiling of STAT3-DNA interactions in keloid fibroblasts. Genome Sequence Archive for Human (GSA-Human). https:\/\/ngdc.cncb.ac.cn\/gsa-human\/browse\/HRA018419. Deposited 11 May 2026."},{"key":"e_1_3_5_53_2","unstructured":"L. Pan D. Li SNHG26 orchestrates mesenchymal fibroblast maintenance via PTBP1-mediated alternative polyadenylation of AKT3 in dermal fibrosis. National Genomics Data Center. https:\/\/ngdc.cncb.ac.cn\/gsa\/browse\/CRA030841. Deposited 4 October 2025."},{"key":"e_1_3_5_54_2","unstructured":"X. Ren Snhg26-mouse. GitHub. https:\/\/github.com\/dazhetang\/snhg26-mouse. Deposited 9 October 2025."},{"key":"e_1_3_5_55_2","unstructured":"L. Pan D. Li Identification of SNHG26-binding proteins in keloid-derived fibroblasts by RNA pull-down and LC-MS\/MS. PRIDE. https:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD068776. 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