{
  "abstract": "Introduction Skin fibrosis, a key feature of systemic sclerosis (SSc) and keloids, involves shared pathological mechanisms—chronic fibroblast activation and excessive extracellular matrix (ECM) deposition. To uncover conserved drivers, we compared scRNA-seq data from SSc, and keloid tissues, aiming to identify unified shared mechanisms and therapeutic targets for fibrotic skin diseases.Material and Methods Using scRNA-seq and functional assays, we analyzed CLEC3B (C-type lectin domain family 3 member B) expression in fibrotic fibroblast subpopulations (SFRP2+ in SSc; CTHRC1+ in keloid). Western blot and immunofluorescence (IF) were employed to assess CLEC3B levels. Functional studies included gene knockout, overexpression, and recombinant protein treatments in vitro and in vivo (bleomycin (BLM)-induced murine fibrosis and keloid xenograft models). A dissolving microneedle delivery system (MNDS) was developed for localized CLEC3B delivery in fibrosis explants.Results CLEC3B was markedly downregulated in key fibrotic fibroblast subpopulations fibrotic fibroblasts (SSc: log2Foldchange = -1.105; keloid: log2Foldchange = -1.640). IF and immunohistochemistry (IHC) confirmed reduced CLEC3B levels at fibrotic sites. In vitro, CLEC3B overexpression suppressed SSc patient fibroblast (SSH) activation and ECM synthesis (e.g., COL1, FN1), while knockout in HFF-1 (Human Foreskin Fibroblast-1) exacerbated fibrotic pathways. In BLM models, Clec3b overexpression attenuated skin fibrosis, decreasing dermal thickness and collagen deposition. Recombinant CLEC3B (rhCLEC3B) reduced scar weight and fibrosis severity in keloid xenografts. RNA sequencing revealed that CLEC3B modulates fibrosis through the Wnt beta-catenin signaling pathway: knockdown in HFF-1 activated this pathway, whereas overexpression in SSH inhibited it. Furthermore, localized delivery of rhCLEC3B using MNDS (Microneedle Drug Delivery System) demonstrated therapeutic efficacy in skin fibrosis explants.Conclusions CLEC3B plays a pivotal role in the regulation of skin fibrosis by modulating fibroblast activation and ECM deposition through the Wnt beta-catenin pathway, as demonstrated in our multi-model validation studies. The successful application of a microneedle delivery system for CLEC3B-targeted therapy presents a practical approach for localized treatment of fibrotic skin conditions.Abstract P.025 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Fudan University, Shanghai, China"
      ],
      "name": "Qianqian Ma"
    },
    {
      "affiliations": [
        "Fudan University, Shanghai, China"
      ],
      "name": "Qingmei Liu"
    },
    {
      "affiliations": [
        "Greater Bay Area Institute of Precision Medicine, Guangzhou, China"
      ],
      "name": "Weilin Pu"
    },
    {
      "affiliations": [
        "Fudan University, Shanghai, China"
      ],
      "name": "Jiucun Wang"
    },
    {
      "affiliations": [
        "Fudan University, Shanghai, China"
      ],
      "name": "Yuhong Liu"
    }
  ],
  "title": "P.025 CLEC3B is a key regulator and potential therapeutic target in skin fibrosis",
  "uid": "66221980-b2a5-56f8-97d3-ec02d43b3c08"
}