Jun Li

Background: Androgenic alopecia (AGA) is a common hair follicle miniaturization disease driven by androgens. Fibroblasts, especially dermal papilla (DP) cells, are considered the core of the pathogenesis of AGA, but there is a lack of systematic synthesis of evidence. Objective: To systematically review the role of fibroblasts (DP cells and dermal sheath cells) in the pathogenesis of AGA, with a focus on androgen signaling transduction, paracrine signaling, disruption of stem cell niche, inflammation, and fibrosis. Data sources: PubMed and Web of Science, covering the period from August 23, 2025 to May 28, 2026, including human basic research, animal model studies, and clinical pathology studies related to AGA fibroblast function. Two reviewers independently screened literature, extracted data, and evaluated the risk of bias. Result: Through retrieval, a total of 1592 articles were identified, and 43 articles were ultimately included. DP cells consistently express high levels of androgen receptor (AR) and 5α-reductase type II. Activation of androgens (dihydrotestosterone) in DP cells leads to: (1) downregulation of Wnt/β-catenin signaling and upregulation of TGF-β/BMP pathway; (2) Changes in secretion profile (decrease in VEGF/IGF-1 and increase in DKK-1/TGF-β1); (3) DP cell aggregation behavior is impaired; (4) Destruction of hair follicle stem cell activation; (5) Inducing inflammation and fibrosis around hair follicles. The evidence for dermal sheath cells as a DP cell bank is still limited. Conclusion: DP cells are the main transducers of androgen signaling in AGA, driving follicle miniaturization through multiple interrelated mechanisms. The current evidence supports DP cell dysfunction as a therapeutic strategy.

Background: Hypertrophic scars are a major clinical challenge with limited treatments. In this study, the therapeutic potential of adipose-derived stem cell peptide 5 (ADSCP5), a novel peptide from adipose-derived stem cell-conditioned medium, was investigated. Methods: We used in vitro hypertrophic scar fibroblast, macrophage–fibroblast coculture and human umbilical vein endothelial cell (HUVEC) assays, RNA sequencing, pathway analysis, peptide pull-down, molecular docking, cellular thermal shift assays, surface plasmon resonance, immunofluorescence colocalization analysis, western blotting, rescue experiments, reactive oxygen species (ROS), autophagy tests, and mitochondrial membrane potential assays and untargeted metabolomics. The efficacy of ADSCP5 was validated in rabbit and porcine scar models. Results: In hypertrophic scar fibroblasts, ADSCP5 significantly downregulated the expression of collagen genes (COL1A1, COL1A2, and COL3A1) and actin alpha 2, smooth muscle (ACTA2) without affecting cell proliferation, apoptosis, or migration. Transcriptomic, enrichment and western blot analyses confirmed that ADSCP5 reduced the protein levels of phosphorylated p65 (p-p65, NF-κB subunit), p-PI3K, p-AKT, and p-mTOR. Moreover, ADSCP5 decreased IL-6 transcription. Mechanistically, ADSCP5 bound directly to pyruvate carboxylase (PC) or the NF-κB subunit p50. This interaction resulted in the downregulation of PC or the upregulation of p50, ultimately inhibiting collagen expression, a finding confirmed by rescue assays. Furthermore, ADSCP5 induced reactive oxygen species (ROS) generation and autophagy, altered global metabolism, and modulated macrophage–fibroblast crosstalk to suppress fibrosis. It also exhibited antiangiogenic effects in HUVECs. In both the rabbit and porcine scar models, ADSCP5 treatment effectively attenuated collagen deposition and scar hyperplasia, increased the number of macrophages (increased CD68), reduced angiogenesis (decreased VEGFA and CD34), and promoted autophagy (reduced p62). Conclusion: Overall, the results of this study demonstrate that ADSCP5 alleviates hypertrophic scarring by directly binding to PC and p50, suppressing the PI3K/AKT/mTOR and NF-κB pathways, reducing IL-6 and collagen production, promoting ROS and autophagy, and modulating metabolic, macrophage and angiogenic responses. These findings position ADSCP5 as a promising therapeutic agent for hypertrophic scar prevention and treatment.

Psoriasis is an inflammatory disorder characterized by scaly erythematous plaques and significant comorbidities. Recent studies have suggested that impaired mitophagy, the cellular mechanism for removing dysfunctional mitochondria, may contribute to the pathogenesis of psoriasis. In this study, we analyzed bulk RNA sequencing data from 167 healthy individuals and 177 patients with psoriasis obtained from the Gene Expression Omnibus database (GSE30999 and GSE54456). Mitophagy-related genes were isolated using weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed and protein-protein interaction networks were constructed for the functional enrichment of genes associated with mitophagy. The correlations between genes associated with mitophagy, signaling pathways, and immune cell infiltration were analyzed. The potential diagnostic value of genes associated with mitophagy was evaluated using receiver operating characteristic (ROC) curves, which were validated in imiquimod-induced psoriatic skin lesions in mice. We identified 3,839 differentially expressed genes between healthy individuals and patients with psoriasis, and 23 genes were selected as hub genes showing a high correlation with mitophagy in psoriasis. GO and KEGG analyses revealed that hub and associated genes were significantly correlated with skin functions, such as epidermal development and keratinocyte differentiation. In addition, mitophagy-related genes were negatively associated with pro-inflammatory and pro-proliferation pathways in psoriasis. Among the immune cells, CD4+ T cells were most significantly affected by mitophagy-related genes. ROC analysis demonstrated that mitophagy-related genes, especially ACER1, C1ORF68, CST6, FLG2, GJB3, GJB5, GPRIN2, KRT2, and SPRR4 were potential biomarkers of psoriasis for use in diagnosis or treatment. Mitophagy-related genes play crucial roles in psoriasis and have potential use as biomarkers, providing insights into disease mechanisms and therapeutic targets. Further research may lead to the development of new strategies for psoriasis management.

Lactylation (Kla), a recently discovered post-translational modification derived from lactate, plays crucial roles in various cellular processes. However, the specific influence of lactylation on the biological processes underlying hypertrophic scar formation remains unclear. In this study, we present a comprehensive profiling of the lactylome and proteome in both hypertrophic scars and adjacent normal skin tissues. A total of 1023 Kla sites originating from 338 nonhistone proteins were identified based on lactylome analysis. Proteome analysis in hypertrophic scar and adjacent skin samples revealed the identification of 2008 proteins. It is worth noting that Kla exhibits a preference for genes associated with ribosome function as well as glycolysis/gluconeogenesis in both normal skin and hypertrophic scar tissues. Furthermore, the functional enrichment analysis demonstrated that differentially lactyled proteins are primarily involved in proteoglycans, HIF-1, and AMPK signaling pathways. The combined analysis of the lactylome and proteome data highlighted a significant upregulation of 14 lactylation sites in hypertrophic scar tissues. Overall, our investigation unveiled the significant involvement of protein lactylation in the regulation of ribosome function as well as glycolysis/gluconeogenesis, potentially contributing to the formation of hypertrophic scars.

Aim: The purpose of this study was to investigate the function and mechanism of a novel peptide derived from adipose‐derived stem cell‐conditioned medium (ADSC‐CM).Methods: Mass spectrometry was applied to identify expressed peptides in ADSC‐CM obtained at different time points. The cell counting kit‐8 assay and quantitative reverse transcription polymerase chain reactions were performed to screen the functional peptides contained within ADSC‐CM. RNA‐seq, western blot, a back skin excisional model of BALB/c mice, the peptide pull‐down assay, rescue experiments, untargeted metabolomics, and mixOmics analysis were performed to thoroughly understand the functional mechanism of selected peptide.Results: A total of 93, 827, 1108, and 631 peptides were identified in ADSC‐CM at 0, 24, 48, and 72 h of conditioning, respectively. A peptide named ADSCP2 (DENREKVNDQAKL) derived from ADSC‐CM inhibited collagen and ACTA2 mRNAs in hypertrophic scar fibroblasts. Moreover, ADSCP2 facilitated wound healing and attenuated collagen deposition in a mouse model. ADSCP2 bound with the pyruvate carboxylase (PC) protein and inhibited PC protein expression. Overexpressing PC rescued the reduction in collagen and ACTA2 mRNAs caused by ADSCP2. Untargeted metabolomics identified 258 and 447 differential metabolites in the negative and positive mode, respectively, in the ADSCP2‐treated group. The mixOmics analysis, which integrated RNA‐seq and untargeted metabolomics data, provided a more holistic view of the functions of ADSCP2.Conclusion: Overall, a novel peptide derived from ADSC‐CM, named ADSCP2, attenuated hypertrophic scar fibrosis in vitro and in vivo, and the novel peptide ADSCP2 might be a promising drug candidate for clinical scar therapy.

Previous studies have demonstrated the involvement of long intergenic nonprotein coding RNA 173 (LINC00173) in several pathological disorders. However, the function of LINC00173 in the hypertrophic scar is not well understood. This study confirmed that the two transcript variants of TSV1 and TSV2 were both upregulated in hypertrophic scar fibroblasts. The overexpression of TSV1 or TSV2 promoted the apoptosis of fibroblasts, whereas the overexpression of TSV2 inhibited the proliferation of fibroblasts. RNA-sequencing (RNA-seq), Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA) showed that phosphatidylinositol 3-kinase (PI3K)/Akt and Mitogen-activated protein kinases (MAPK) signaling might be involved in the role of LINC00173 in hypertrophic scar pathogenesis. Furthermore, the protein expression of β-catenin was upregulated in the TSV1 or TSV2 overexpression group. Overall, the study demonstrated that LINC00173 promoted the apoptosis of fibroblasts through increasing β-catenin expression, suggesting that LINC00173 might be a new target for hypertrophic scar treatment.