Human Tubular Epithelial Cells Activate a Coordinated Stress Response after Serum Exposure [RNAseq-pid1830]

Proteinuria, the spillage of serum proteins into the urine, is a feature of glomerulonephritides, podocyte disorders and diabetic nephropathy. However, the response of tubular epithelial cells to serum protein exposure has not been systematically characterized. Using transcriptomic profiling we studied serum-induced changes in primary human tubular epithelial cells cultured in 3D microphysiological devices. Serum proteins induced cellular proliferation, secretion of cytokines and activated a coordinated stress response. We orthogonally confirmed our findings by comparing the transcriptomic and epigenomic landscapes of. Importantly, key transcriptomic programs in response to serum exposure remained consistent when comparing intact renal cortex to primary human tubules cultured in 10% fetal bovine serum and to an established mouse model of kidney injury. This serum-induced transcriptional response was dominated by AP-1 and NFkB signatures in the tubular epigenomic landscape with features of active regulation at canonical kidney injury genes (HAVCR1) and genes associated with COVID-19 (ACE2, IL6). Our data provide a reference map for dissecting the regulatory and transcriptional response of tubular epithelial cells to serum-induced injury. Kidney MPS were exposed to maintenance media or maintenance media spiked with 2% normal human serum (~720 ug/mL albumin equivalent) for 48 hours.