{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:01:59Z","timestamp":1781013719293,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Hallym University Research Fund","doi-asserted-by":"publisher","award":["RS-202300243252"],"award-info":[{"award-number":["RS-202300243252"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Slit1 is a secreted protein that is closely related to cell movement and adhesion. Few studies related to fibrosis exist, and the preponderance of current research is confined to the proliferation and differentiation of neural systems. Hypertrophic scars (HTSs) are delineated by an overproduction of the extracellular matrix (ECM) by activated fibroblasts, leading to anomalous fibrosis, which is a severe sequela of burns. However, the functionality of Slit1 in HTS formation remains unknown. We aimed to investigate whether Slit1 regulates fibroblasts through a fibrosis-related mechanism derived from post-burn HTS tissues and normal patient tissues. Methods: Human normal fibroblasts (HNFs) and hypertrophic scar fibroblasts (HTSFs) were extracted from normal skin and post-burn HTS tissues, with settings grouped according to the patient of origin. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. Cell migration experiments were carried out using a \u03bc-Dish insert system. Protein and mRNA expression levels were quantified by Western blot and quantitative real-time polymerase chain reaction. Results: We found increased expressions of Slit1 in HTS tissues and HTSFs compared to normal tissues and HNFs. The treatment of human recombinant Slit1 protein (rSlit1) within HNFs promoted cell proliferation and differentiation, leading to an upregulation in ECM components such as \u03b1-SMA, type I and III collagen, and fibronectin. The treatment of rSlit1 in HNFs facilitated cell migration, concurrent with enhanced levels of N-cadherin and vimentin, and a diminished expression of E-cadherin. Treatment with rSlit1 resulted in the phosphorylation of SMAD pathway proteins, including SMAD2, SMAD3, and SMAD1\/5\/8, and non-SMAD pathway proteins, including TAK1, JNK1, ERK1\/2, and p38, in HNFs. Conclusions: Exogenous Slit1 potentiates the epithelial\u2013mesenchymal transition and upregulates SMAD and non-SMAD signaling pathways in HNFs, leading to the development of HTS, suggesting that Slit1 is a promising new target for the treatment of post-burn HTS.<\/jats:p>","DOI":"10.3390\/medicina60122051","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T10:53:27Z","timestamp":1734000807000},"page":"2051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Slit1 Promotes Hypertrophic Scar Formation Through the TGF-\u03b2 Signaling Pathway"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-1838","authenticated-orcid":false,"given":"Hui Song","family":"Cui","sequence":"first","affiliation":[{"name":"Burn Institute, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Burn Institute, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9959-3285","authenticated-orcid":false,"given":"Yoon Soo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Mi","family":"Ro","sequence":"additional","affiliation":[{"name":"Burn Institute, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-5366","authenticated-orcid":false,"given":"Kibum","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-6382","authenticated-orcid":false,"given":"Cheong Hoon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 94-200 Yeongdeungpo-Dong, Yeongdeungpo-Ku, Seoul 07247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.59249\/RHUF5686","article-title":"The Molecular Mechanisms Involved in the Hypertrophic Scars Post-Burn Injury","volume":"96","author":"Pradhan","year":"2023","journal-title":"Yale J. 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