Angiomotin mutation causes glomerulopathy and renal cysts by upregulating hepatocyte nuclear factor transcriptional activity

Single-cell RNA sequencing (RNA-Seq) revealed relatively high transcriptional levels of AMOT in podocyte and proximal tubule segment S1 cells. [...]to decipher disease pathogenesis, RNA-Seq was performed on freshly isolated PCT cells since they are more easily isolated than podocytes. The importance of HNF4α activation to the PG phenotype is further supported by stress fiber formation and altered ZO-1 distribution when kidney cell lines are treated with Benfluorex, a known HNF4α activator (Figure S8).7 Considering that the GSEA of the differentially expressed genes revealed metabolic pathway alterations, we performed metabolic profiling of the rat plasma as an exploratory analysis to identify the metabolic pathways involved (Figure 4A). [...]we report a putative novel role of AMOT in causing glomerulotubular nephropathy in patients and rats, possibly by regulating the HNF4α pathway and the subsequent metabolic pathways.