Proliferation and osmotic tolerance of renal inner medullary epithelial cells in vivo and in cell culture.
Renal inner medullary (IM) cells survive interstitial osmolality that ranges from 600 to 1,700 mosmol/kgH2O or more. In contrast, much smaller acute changes killed the cells previously studied in tissue culture, such as mouse IM collecting duct 3 (mIMCD3) cells, that are immortalized with SV40 and proliferate rapidly. Proliferation and DNA replication sensitize mIMCD3 cells to hypertonicity. In the present studies, we observed that proliferating cells were scarce in rat IM. Then, we prepared passage 2 mouse IM epithelial (p2mIME) cells. They have a much lower incidence of DNA replication than do mIMCD3 cells. p2mIME cells survive much greater acute increases in NaCl than do mIMCD3 cells and also tolerate significantly greater acute increases of urea and of NaCl plus urea, but still not to levels as high as occur in vivo. We conclude that immortalization and continued DNA replication account for part of the previously observed difference in osmotic tolerance between IM cells in vivo and in cell culture but that other factors must also be involved.
Laboratory of Kidney and Electrolyte Metabolism, National Heart Lung and Blood Institute, Bethesda, Maryland 20892, USA. Zhangz@nhlbi.nih.gov
Zheng
Z
Zhang
Qi
Q
Cai
Luis
L
Michea
Natalia I
NI
Dmitrieva
Peter
P
Andrews
Maurice B
MB
Burg
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D007679:Kidney Medulla / Q000166:cytology* / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000166:cytology; D008297:Male; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D014508:Urea / Q000378:metabolism / Q000494:pharmacology; D014868:Water Deprivation / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000502:physiology*
D018809:Proliferating Cell Nuclear Antigen; D012965:Sodium Chloride; D014508:Urea