(Pro)renin receptor mediates albumin-induced cellular responses: role of site-1 protease-derived soluble (pro)renin receptor in renal epithelial cells
| العنوان: | (Pro)renin receptor mediates albumin-induced cellular responses: role of site-1 protease-derived soluble (pro)renin receptor in renal epithelial cells |
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| المؤلفون: | Yanting Chen, Li Zhou, Weidong Wang, Chuanming Xu, Tianxin Yang, Chang Jiang Zou, Hui Fang, Lei Wang, Mi Liu, Shiying Xie, Aihua Lu |
| المصدر: | American Journal of Physiology-Cell Physiology. 313:C632-C643 |
| بيانات النشر: | American Physiological Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Vacuolar Proton-Translocating ATPases, medicine.medical_specialty, Physiology, Pro renin receptor, Receptors, Cell Surface, Serum Albumin, Human, 030204 cardiovascular system & hematology, Biology, Kidney, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Renin–angiotensin system, medicine, Humans, RNA, Small Interfering, Cell Line, Transformed, Proteinuria, Serine Endopeptidases, Disease progression, Albumin, Epithelial Cells, Cell Biology, Site-1 protease, medicine.disease, 030104 developmental biology, Endocrinology, Proprotein Convertases, medicine.symptom, Corrigendum, Kidney disease |
| الوصف: | Proteinuria is a characteristic of chronic kidney disease and also a causative factor that promotes the disease progression, in part, via activation of the intrarenal renin-angiotensin system (RAS). (Pro)renin receptor (PRR), a newly discovered component of the RAS, binds renin and (pro)renin to promote angiotensin I generation. The present study was performed to test the role of soluble PRR (sPRR) in albumin overload-induced responses in cultured human renal proximal tubular cell line human kidney 2 (HK-2) cells. Bovine serum albmuin (BSA) treatment for 24 h at 20 mg/ml induced renin activity and inflammation, both of which were attenuated by a PRR decoy inhibitor PRO20. BSA treatment induced a more than fivefold increase in medium sPRR due to enhanced cleavage of PRR. Surprisingly, this cleavage event was unaffected by inhibition of furin or a disintegrin and metalloproteinase 19. Screening for a novel cleavage enzyme led to the identification of site-1 protease (S1P). Inhibition of S1P with PF-429242 or siRNA remarkably suppressed BSA-induced sPRR production, renin activity, and inflammatory response. Administration of a recombinant sPRR, termed sPRR-His, reversed the effects of S1P inhibition. In HK-2 cells overexpressing PRR, mutagenesis of the S1P, but not furin cleavage site, reduced sPRR levels. Together, these results suggest that PRR mediates albumin-induced cellular responses through S1P-derived sPRR. |
| تدمد: | 1522-1563 0363-6143 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab7049fe1bc394d2d379825e44388c0e https://doi.org/10.1152/ajpcell.00006.2017 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ab7049fe1bc394d2d379825e44388c0e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
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