{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:53:23Z","timestamp":1783644803423,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["HI15C0001"],"award-info":[{"award-number":["HI15C0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The clinical aspects of hypertrophic scarring vary according to personal constitution and body part. However, the mechanism of hypertrophic scar (HS) formation remains unclear. MicroRNAs (miRNAs) are known to contribute to HS formation, however, their detailed role remains unknown. In this study, candidate miRNAs were identified and analyzed as biomarkers of hypertrophic scarring for future clinical applications. HSfibroblasts and normal skin fibroblasts from patients were used for profiling and validation of miRNAs. An HS mouse model with xenografted human skin on nude mice was established. The miRNA expression between normal human, normal mouse, and mouse HS skin tissues was compared. Circulating miRNA expression levels in the serum of normal mice and mice with HSs were also analyzed. Ten upregulated and twenty-one downregulated miRNAs were detected. Among these, miR-365a\/b-3p and miR-16-5p were identified as candidate miRNAs with statistically significant differences; miR-365a\/b-3p was significantly upregulated (p = 0.0244). In mouse studies, miR-365a\/b-3p expression levels in skin tissue and serum were higher in mice with HSs than in the control group. These results indicate that miRNAs contribute to hypertrophic scarring and that miR-365a\/b-3p may be considered a potential biomarker for HS formation.<\/jats:p>","DOI":"10.3390\/ijms23116117","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T10:05:14Z","timestamp":1653905114000},"page":"6117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MicroRNA-365a\/b-3p as a Potential Biomarker for Hypertrophic Scars"],"prefix":"10.3390","volume":"23","author":[{"given":"Joon Seok","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3795-4735","authenticated-orcid":false,"given":"Gyeonghwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41199, Korea"},{"name":"CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-5051","authenticated-orcid":false,"given":"Jeong","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-9870","authenticated-orcid":false,"given":"Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-4836","authenticated-orcid":false,"given":"Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suin","family":"Kwak","sequence":"additional","affiliation":[{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41199, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-2718","authenticated-orcid":false,"given":"Keun","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41199, Korea"},{"name":"CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41199, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-3044","authenticated-orcid":false,"given":"Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea"},{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41199, Korea"},{"name":"Kyungpook National University Bio-Medical Research Institute, Kyungpook National University, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lee, H.J., and Jang, Y.J. (2018). Recent Understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030711"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s12079-013-0195-5","article-title":"The molecular mechanism of hypertrophic scar","volume":"7","author":"Zhu","year":"2013","journal-title":"J. Cell Commun. Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.yexcr.2017.09.009","article-title":"Study on the role of Hsa-miR-31-5p in hypertrophic scar formation and the mechanism","volume":"361","author":"Wang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Aarabi, S., Longaker, M.T., and Gurtner, G.C. (2007). Hypertrophic scar formation following burns and trauma: New approaches to treatment. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040234"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1159\/000493236","article-title":"miR-137 inhibits proliferation and metastasis of hypertrophic scar fibroblasts via targeting pleiotrophin","volume":"49","author":"Zhang","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1111\/j.1524-475X.2007.00219.x","article-title":"Cellular and molecular pathology of HTS: Basis for treatment","volume":"15","author":"Armour","year":"2007","journal-title":"Wound Repair Regen."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.cellbio.23.090506.123609","article-title":"Transcriptional control of wound repair","volume":"23","author":"Werner","year":"2007","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.cclet.2019.09.011","article-title":"Whole wheat flour coating with antioxidant property accelerates tissue remodeling for enhanced wound healing","volume":"31","author":"Xian","year":"2020","journal-title":"Chin. Chem. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"134690","DOI":"10.1016\/j.cej.2022.134690","article-title":"1D, 2D, and 3D scaffolds promoting angiogenesis for enhanced wound healing","volume":"437","author":"Guo","year":"2022","journal-title":"Chem. Eng. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S0039-6109(05)70576-4","article-title":"Hypertrophic scars, keloids, and contractures. The cellular and molecular basis for therapy","volume":"77","author":"Tredget","year":"1997","journal-title":"Surg. Clin. North. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.biocel.2015.06.009","article-title":"microRNA-365-targeted nuclear factor I\/B transcriptionally represses cyclin-dependent kinase 6 and 4 to inhibit the progression of cutaneous squamous cell carcinoma","volume":"65","author":"Zhou","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, M., Zhou, L., and Zheng, L. (2014). miR-365 promotes cutaneous squamous cell carcinoma (CSCC) through targeting nuclear factor I\/B (NFIB). PLoS ONE., 9.","DOI":"10.1371\/journal.pone.0100620"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00403-013-1410-1","article-title":"The role of microRNAs in skin fibrosis","volume":"305","author":"Babalola","year":"2013","journal-title":"Arch. Dermatol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.yexcr.2015.10.018","article-title":"Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars","volume":"339","author":"Zhou","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.yexcr.2016.05.013","article-title":"Fibroproliferative effect of microRNA-21 in hypertrophic scar derived fibroblasts","volume":"345","author":"Li","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/carcin\/bgr245","article-title":"microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2","volume":"33","author":"Nie","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/carcin\/bgt097","article-title":"A novel onco-miR-365 induces cutaneous squamous cell carcinoma","volume":"34","author":"Zhou","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1038\/ncomms3544","article-title":"Akt-p53-miR-365-cyclin D1\/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency","volume":"4","author":"Guo","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_20","first-page":"1568","article-title":"Downregulation of BCL2 by miRNAs augments drug-induced apoptosis\u2014A combined computational and experimental approach","volume":"125","author":"Singh","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cellsig.2013.11.003","article-title":"MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX","volume":"26","author":"Hamada","year":"2014","journal-title":"Cell Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.3892\/or.2016.4617","article-title":"MicroRNA-365a-3p promotes tumor growth and metastasis in laryngeal squamous cell carcinoma","volume":"35","author":"Geng","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/MAJ.0b013e318267680d","article-title":"Identification of collagen 1 as a posttranscriptional target of miR-29b in skin fibroblasts: Therapeutic implication for scar reduction","volume":"346","author":"Cheng","year":"2013","journal-title":"Am. J. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1365-2133.2010.10048.x","article-title":"Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: Clinical implications for lesional site-directed therapy","volume":"164","author":"Syed","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3892\/mmr.2013.1278","article-title":"Suppression of cell proliferation and collagen production in cultured human hypertrophic scar fibroblasts by Sp1 decoy oligodeoxynucleotide","volume":"7","author":"Deng","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1524-475X.2012.00856.x","article-title":"A nude mouse model of hypertrophic scar shows morphologic and histologic characteristics of human hypertrophic scar","volume":"21","author":"Momtazi","year":"2013","journal-title":"Wound Repair Regen."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1524-475X.2011.00672.x","article-title":"Human hypertrophic scar-like nude mouse model: Characterization of the molecular and cellular biology of the scar process","volume":"19","author":"Wang","year":"2011","journal-title":"Wound Repair Regen."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.3760\/cma.j.issn.0366-6999.20130833","article-title":"Pressure therapy upregulates matrix metalloproteinase expression and downregulates collagen expression in hypertrophic scar tissue","volume":"126","author":"Huang","year":"2013","journal-title":"Chin. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1096\/fj.11-185132","article-title":"MiR-365: A mechanosensitive microRNA stimulates chondrocyte differentiation through targeting histone deacetylase 4","volume":"25","author":"Guan","year":"2011","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, Z., Zhang, Y., Liang, C., Chen, L., Zhang, G., and Qian, A. (2017). Mechanosensitive miRNAs and bone formation. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081684"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bbrc.2017.01.108","article-title":"MicroRNA-365 accelerates cardiac hypertrophy by inhibiting autophagy via the modulation of Skp2 expression","volume":"484","author":"Wu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wehbe, N., Nasser, S.A., Pintus, G., Badran, A., Eid, A.H., and Baydoun, E. (2019). MicroRNAs in Cardiac Hypertrophy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194714"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/nrg2628","article-title":"Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications","volume":"10","author":"Brown","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_34","first-page":"4952","article-title":"Resveratrol transcriptionally regulates miRNA-18a-5p expression ameliorating diabetic nephropathy via increasing autophagy","volume":"21","author":"Xu","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"296","DOI":"10.2119\/molmed.2014.00172","article-title":"miR-145 contributes to hypertrophic scarring of the skin by inducing myofibroblast activity","volume":"21","author":"Gras","year":"2015","journal-title":"Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/gutjnl-2014-308737","article-title":"Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer","volume":"66","author":"Hur","year":"2017","journal-title":"Gut"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:21:54Z","timestamp":1760138514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,30]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116117"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116117","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,30]]}}}