Omics · study · 2026
Downregulating CHI3L2 via the STAT3 Pathway: The Mechanism of Calcitriol in Suppressing Psoriatic Inflammation and Keratinocyte Hyperproliferation
Listed in NCBI GEO
Psoriasis is a chronic inflammatory skin disorder driven by immune dysregulation and keratinocyte hyperproliferation.
Description
Calcitriol, the active form of vitamin D, shows therapeutic potential, but its molecular mechanisms remain incompletely understood. Here, we investigated the role of CHI3L2 in mediating the anti-psoriatic effects of calcitriol.
Topical application of calcitriol alleviated imiquimod (IMQ)-induced psoriasiform lesions in both unilateral and bilateral mouse ear models, as evidenced by reduced clinical scores, epidermal thickening, and pro-inflammatory cytokine expression (IL-1α, IL-6, IL-17A, IL-23A). In M5-stimulated HaCaT cells, calcitriol reversed aberrant proliferation, migration, and inflammatory responses, and restored keratin expression (KRT1/KRT6).
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RNA-seq identified CHI3L2 as the most significantly downregulated gene following calcitriol treatment. CHI3L2 knockdown phenocopied the protective effects of calcitriol, suppressing cell proliferation, migration, and inflammation. Mechanistically, calcitriol downregulated CHI3L2 via inhibition of STAT3 phosphorylation at Ser727.
Collectively, these findings demonstrate that calcitriol ameliorates psoriatic inflammation and keratinocyte hyperproliferation through CHI3L2 downregulation mediated by the STAT3 pathway, highlighting CHI3L2 as a potential therapeutic target for psoriasis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327525 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327525 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1451170 ncbi.nlm.nih.gov/bioproject/PRJNA1451170 ↗
project · from NCBI GEO
- PubMed 42747744 pubmed.ncbi.nlm.nih.gov/42747744 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE327525 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |