Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 315, Issue 2, Pages F332-F335Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00126.2018
Keywords
3D in vitro culture; ADPKD; organoid; polycystin; stem cell
Categories
Funding
- National Kidney Foundation of Maryland
- National Institute of General Medical Sciences (NIGMS) [5T32GM008181]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30DK090868]
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Novel technologies, new understanding of the basement membrane composition, and better comprehension of the embryonic development of the mammalian kidney have led to explosive growth in the use of three-dimensional in vitro models to study a range of human disease pathologies (Clevers H. Cell 165: 1586-1597, 2016; Shamir ER, Ewald AJ. Nat Rev Mol Cell Biol 15: 647-664, 2014). The development of these effective model systems represents a new tool to study the progressive cystogenesis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a prevalent and complex monogenetic disease, characterized by the pathological formation of fluid fill cysts in renal tissue (Grantham JJ, Mulamalla S, Swenson-Fields KI. Nat Rev Nephrol 7: 556-566, 2011; Takiar V, Caplan MJ. Biochim Biophys Acta 1812: 1337-1343, 2011). ADPKD cystogenesis is attributed to loss of function mutations in either PKD1 or PKD2, which encode for two transmembrane proteins, polycystin-1 and polycystin-2, and progresses with loss of both copies of either gene through a proposed two-hit mechanism with secondary somatic mutations (Delmas P, Padilla F, Osorio N, Coste B, Raoux M, Crest M. Biochem Biophys Res Commun 322: 1374-1383, 2004; Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St George-Hyslop P. Am Soc Nephrol 10: 1524-1529, 1999; Wu G, D'Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H Jr, Kucherlapati R, Edelmann W, Somlo S. Cell 93: 177-188, 1998). The exaggerated consequences of large fluid filled cysts result in fibrosis and nephron injury, leading initially to functional compensation but ultimately to dysfunction (Grantham JJ. Am J Kidney Dis 28: 788-803, 1996; Norman J. Biochim Biophys Acta 1812: 1327-1336, 2011; Song CJ, Zimmerman KA, Henke SJ, Yoder BK. Results Probl Cell Differ 60: 323-344, 2017). The complicated disease progression has scattered focus and resources across the spectrum of ADPKD research.
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