Data · study · 2026
Complement Factor H maintains macrophage homeostasis through TRPM7 signaling
Listed in NCBI GEO
Factor H (FH) is a critical regulator of the alternative complement pathway preventing uncontrolled complement activation.
Description
Its role in mitigating complement-mediated injury is evident in diseases such as dense deposit disease and age related macular degeneration characterized by significant macrophage (Mo) infiltration. While primarily synthesized in the liver, FH is also produced by other cells, including monocytes and Mos.
However, the influence of FH on these cells remains incompletely understood. This study explores the functions of FH in rodent bone marrow-derived Mos, revealing FH-dependent regulation of genes linked to proliferation and inflammation, including C3aR, the receptor for C3a generated on complement activation. Further, our findings demonstrate that intrinsic FH deficiency in Mos enhances proliferation, trafficking, migration, and reduces phagocytosis.
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FH-deficient Mos exhibit metabolic alterations characterized by reduced oxidative phosphorylation and glycolysis. Notably, our results show for the first time that FH in Mos influences non-canonical functions through downstream C3a/C3aR signaling, modulating calcium levels and the activity of transient receptor potential cation channel, subfamily M, member 7 (TRPM7). Inhibiting TRPM7 activity with FTY720 reduces Mo proliferation, and blocking C3a/C3aR signaling mitigates TRPM7-related alterations and proliferation in Mos.
In summary, this study highlights FH's functional relevance in maintaining homeostasis in Mos, where it modulates functions in a cell-autonomous manner, regulating TRPM7 through C3a/C3aR signaling pathways, offering therapeutic avenues for kidney disease and other inflammatory conditions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE279nnn/GSE279157 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279157 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1170995 ncbi.nlm.nih.gov/bioproject/PRJNA1170995 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by array · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE279157 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-array | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | 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 |