Multi-omic Characterization of Human Tubular Epithelial Cell Response to Serum
Multi-omic Characterization of Human Tubular Epithelial Cell Response to Serum
Abstract 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, cytokine secretion and activated a coordinated stress response. We orthogonally confirmed our findings by comparing the transcriptomic and epigenomic landscapes of intact human kidney cortex and isolated tubular epithelial cells cultured in fetal bovine serum. Importantly, key transcriptomic programs in response to either type of serum exposure remained consistent, including comparisons to an established mouse model of kidney injury. This serum-induced transcriptional response was dominated by switching off of nuclear receptor-driven programs and activation of AP-1 and NF-κB signatures in the tubular epigenomic landscape. These features of active regulation were seen 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 kidney tubular epithelial cells injury induced by serum.
Muthusamy Selvaraj、Patel Ranita S.、Bammler Theo K.、Reichel Jonathan、Akilesh Shreeram、Lidberg Kevin A.、Kelly Edward J.、Wang Lu、Yeung Catherine K.、Adil Mohamed、Himmelfarb Jonathan
Department of Laboratory Medicine and Pathology, University of WashingtonSeattle Children?ˉs HospitalDepartment of Environmental and Occupational Health Sciences, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of WashingtonDepartment of Laboratory Medicine and Pathology, University of Washington||Kidney Research InstituteDepartment of Pharmaceutics, University of WashingtonDepartment of Pharmaceutics, University of Washington||Kidney Research InstituteDepartment of Environmental and Occupational Health Sciences, University of WashingtonDepartment of Pharmacy, University of Washington||Kidney Research InstituteDepartment of Laboratory Medicine and Pathology, University of WashingtonKidney Research Institute||Department of Medicine, Nephology Division, University of Washington
基础医学生物科学研究方法、生物科学研究技术生理学
Muthusamy Selvaraj,Patel Ranita S.,Bammler Theo K.,Reichel Jonathan,Akilesh Shreeram,Lidberg Kevin A.,Kelly Edward J.,Wang Lu,Yeung Catherine K.,Adil Mohamed,Himmelfarb Jonathan.Multi-omic Characterization of Human Tubular Epithelial Cell Response to Serum[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2021.01.29.428186.点此复制
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