GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329325/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329325GEOGSEfalseRNA-seq analysis of thick ascending limb (TAL) epithelium isolated from uromodulin (UMOD) deletion mutation and wild type (WT) kidney organoids with or without mesencephalic astrocyte-derived neurotrophic factor (MANF) overexpressionAutosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD) is one of the leading hereditary kidney diseases. Currently there is no targeted treatment. To illuminate human relevance of mesencephalic astrocyte-derived neurotrophic factor (MANF)-based therapy, we have established patient induced pluripotent stem cell (iPSC)-derived kidney organoid model carrying UMOD p.H177-R185del, the leading mutation causing ADTKD. We have discovered that MANF can directly bind and repress ER calcium release channel IP3R1, thus enhancing AMPK-induced autophagy in a TRIB3-dependent manner. The therapeutic implication of this finding may well be extended to other protein misfolding diseases.2026/07/11GSE329325GSM9701783GSM9701784GSM9701781GSM9701782GSM9701776GSM9701777GSM9701785GSM9701786GSM9701775GSM9701778GSM9701779GSM970178034284329325Homo sapiens