. 2025 Aug:238:116980.
doi: 10.1016/j.bcp.2025.116980. Epub 2025 May 8.
Affiliations
PMID: 40348095 DOI: 10.1016/j.bcp.2025.116980
From stem cells to skin: ADSCP6 peptide's role in transforming scar therapy
Jun Li et al. Biochem Pharmacol. 2025 Aug.
Abstract
Hypertrophic scars, caused by abnormal wound healing after injury, involve excessive fibroblast activity, ECM dysregulation, and inflammation. Bioactive peptides show antifibrotic potential. Based on our previous discovery of scar-modulating peptides from adipose-derived stem cells, this study reveals how ADSCP6 (Adipose-derived stem cell peptide 6) suppresses hypertrophic scarring. In vitro analyses revealed that ADSCP6 significantly downregulated type I collagen and ACTA2 (alpha smooth muscle actin) expression in human hypertrophic scar fibroblasts (HSFs), without altering proliferative/apoptotic activity. In vivo, topical ADSCP6 administration enhanced wound healing and attenuated collagen content in a murine excisional wound model. Transcriptomic profiling (RNA-seq) identified 328 differentially expressed genes (182 upregulated, 146 downregulated) post-treatment, with KEGG (kyoto encyclopedia of genes and genomes) pathway enrichment implicating NF-κB (nuclear factor kappa-B) signaling as a primary mechanism. Protein interaction assays (pull-down/cellular thermal shift assays) identified KANK2 (KN motif and ankyrin repeat domains 2) and ADGRE2/EMR2 (adhesion G protein-coupled receptor E2) as ADSCP6-binding partners, while western blot confirmed NF-κB1 (p50) upregulation. Functional validation demonstrated that NF-κB pathway blockade abrogated ADSCP6's antifibrotic effects. ADSCP6 reduced the expression of FAK, STAT3, and SMAD2 proteins. Macrophage-conditioned media from ADSCP6-treated cultures suppressed HSFs collagen synthesis, and ADSCP6 significantly enhanced HUVEC (human umbilical vein endothelial cells) tubulogenesis, suggesting pro-angiogenic activity. Overall, these findings establish ADSCP6 as a multifunctional therapeutic peptide that concurrently attenuates fibrotic progression and accelerates wound healing, positioning it as a novel candidate for clinical scar management.
Keywords: ADSCP6; Fibroblasts; Hypertrophic scar; NF-κB; Peptide.
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Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.