{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330552/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330552"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Interferon regulatory factor 5 in myeloid cells promotes obstructive nephropathy-induced renal fibrosis in vivo","description":"Obstructive nephropathy is a significant and preventable contributor to chronic kidney disease, yet no disease-modifying anti-fibrotic agents are currently available.We hypothesized that interferon regulatory factor 5 (IRF5) functions as a macrophage transcriptional regulator that directly transactivates matrix metalloproteinase 9 (MMP9) to initiate early extracellular matrix (ECM) remodeling. Analysis of 30 human obstructive nephropathy biopsy specimens demonstrated that IRF5+CD68+ macrophage density increased progressively with fibrosis severity and correlated significantly with α-smooth muscle actin (α-SMA) positive areas. In the murine unilateral ureteral obstruction (UUO) model, both global and myeloid-specific Irf5 deletion significantly attenuated collagen deposition, immune cell infiltration, and fibrotic gene expression compared with wild-type controls. Cleavage under targets and tagmentation (CUT&Tag) analysis demonstrated that IRF5 directly binds the Mmp9 enhancer region and increases chromatin accessibility. Consequently, myeloid-specific Irf5 knockout significantly reduced Mmp9 mRNA and MMP9 protein levels. Pharmacological inhibition using the first-in-class IRF5 inhibitor N5-1 mitigated established fibrosis, down-regulated α-SMA and MMP9 expression, and reduced CD68+ macrophage infiltration. These findings identify the IRF5-MMP9 axis as a therapeutically targetable pathway driving macrophage-mediated ECM expansion and provide pre-clinical evidence supporting IRF5 inhibition as a potential treatment strategy for patients with obstructive nephropathy.","dates":{"publication":"2026/07/28"},"accession":"GSE330552","cross_references":{"GSM":["GSM9728770","GSM9728781","GSM9728780","GSM9728772","GSM9728782","GSM9728771","GSM9728774","GSM9728773","GSM9728776","GSM9728765","GSM9728775","GSM9728764","GSM9728778","GSM9728767","GSM9728777","GSM9728766","GSM9728769","GSM9728779","GSM9728768"],"GPL":["34290"],"GSE":["330552"],"taxon":["Mus musculus"]}}