Aquaporin 2-labeled cells differentiate to intercalated cells in response to potassium depletion.
The mammalian renal collecting duct consists of principal cells (PCs) and intercalated cells (ICs). Both PCs and ICs are involved in potassium (K(+)) homeostasis, PCs through their role in K(+) secretion and ICs through their ability to facilitate K(+) resorption. We previously hypothesized that PCs may differentiate into ICs upon K(+) depletion. However, no direct evidence has yet been obtained to conclusively demonstrate that PCs differentiate into ICs in response to K(+) depletion. Here, we present direct evidence for the differentiation of PCs into ICs by cell lineage tracing using aquaporin 2 (AQP2)-Cre mice and R26R-EYFP transgenic mice. In control mice, AQP2-EYFP(+) cells exhibited mainly a PC phenotype (AQP2-positive/H(+)-ATPase-negative). Interestingly, some AQP2-EYFP(+) cells exhibited an IC phenotype (H(+)-ATPase-positive/AQP2-negative); these cells accounted for 1.7 %. After K(+) depletion, the proportion of AQP2-EYFP(+) cells with an IC phenotype was increased to 4.1 %. Furthermore, some AQP2-EYFP(+) cells exhibited a "null cell" phenotype (AQP2-negative/H(+)-ATPase-negative) after K(+) depletion. Collectively, our data demonstrate that AQP2-labeled cells can differentiate into ICs, as well as null cells, in response to K(+) depletion. This finding indicates that some of AQP2-labeled cells possess properties of progenitor cells and that they can differentiate into ICs in the adult mouse kidney.
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea.
Wan-Young
WY
Kim
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea.
Sun Ah
SA
Nam
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea.
Arum
A
Choi
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea.
Yu-Mi
YM
Kim
Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital, Bucheon-si, Korea.
Sang Hee
SH
Park
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea. drkimyk@catholic.ac.kr.|Department of Internal Medicine, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Sosa-ro 327, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-717, Korea. drkimyk@catholic.ac.kr.
Yong Kyun
YK
Kim
Department of Anatomy and Cell Death Disease Research Center, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137-701, Korea. jinkim@catholic.ac.kr.
Jin
J
Kim
D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D007685:Kidney Tubules, Collecting / Q000166:cytology*; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*
C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D011188:Potassium
Aquaporin; Differentiation; Intercalated cells; Principal cell