Omics · study · 2026
Activation of the SRC/MEK/ERK Pathway by Arsenic Disulfide Restores Megakaryopoiesis and Platelet Production in Myelodysplastic Syndrome
Listed in NCBI GEO
Thrombocytopenia is a common and clinically significant complication of myelodysplastic syndrome (MDS), but effective therapies directly targeting megakaryopoiesis are limited.
Description
Sanzi Huangshi Pill (SZHSP), a traditional Chinese medicine formula containing arsenic disulfide (As2S2), has been found to have haematopoietic effects in clinical settings, but the mechanisms involved have yet to be fully explained. In this study, the effects of SZHSP and As2S2 on megakaryocyte differentiation were evaluated in NUP98-HOXD13 transgenic mice and Meg-01 cells.
Through haematological analyses, flow cytometry, molecular assays, network pharmacology, RNA sequencing, and pharmacological inhibition studies, we found that SZHSP significantly improved thrombocytopenia in MDS mice, increased the proportion of mature CD41+CD42+ megakaryocytes, and up-regulated the expression of Gata-1, Fog1, and Fli1. In vitro, both SZHSP-containing serum and As2S2 induced megakaryocytic differentiation and increased lineage-associated markers in Meg-01 cells.
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Transcriptomic analysis and network pharmacology demonstrated the activation of MAPK-related pathways and megakaryopoiesis-associated gene programs, identifying SRC and MAPK signaling as important regulatory nodes. Mechanistic studies further revealed that As2S2 increased the phosphorylation of SRC, MEK, and ERK, and the pharmacological inhibition of SRC significantly reduced the differentiation-promoting effects of As2S2.
In conclusion, SZHSP and its major active ingredient As2S2 promote megakaryocyte differentiation and platelet recovery by activating the SRC/MEK/ERK signaling pathway, offering mechanistic evidence for SZHSP as a potential differentiation-based therapeutic approach for MDS-associated thrombocytopenia.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336313 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336313 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1481242 ncbi.nlm.nih.gov/bioproject/PRJNA1481242 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE336313 | 11 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 (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |