caa a22 4500 445883588 CHVBK 20180317145552.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10157-011-0453-x doi (NATIONALLICENCE)springer-10.1007/s10157-011-0453-x Acquired resistance to rechallenge injury in rats that recovered from mild renal damage induced by uranyl acetate: accelerated proliferation and hepatocyte growth factor/c-Met axis [Elektronische Daten] [Yuan Sun, Yoshihide Fujigaki, Masanori Sakakima, Tomoyuki Fujikura, Akashi Togawa, Yanjie Huang, Akira Hishida] Background: Rats that recovered from mild proximal tubule (PT) injury without renal dysfunction by subtoxic insult, developed partial resistance to subsequent nephrotoxic insult. This partial resistance was associated with reduced renal dysfunction and accelerated PT cell proliferation compared with vehicle treatment as the first insult. Here we assessed the role and potential mechanisms of accelerated PT proliferation in this acquired resistance model. Methods: Rats at 14days after recovering from prior mild renal damage induced by 0.2mg/kg uranyl acetate (UA) (subtoxic dose) were rechallenged with 4mg/kg UA (nephrotoxic dose) to establish the acquired resistance model. Cell cycle was inhibited by colchicine to examine the contribution of accelerated PT cell proliferation evaluated by in vivo bromodeoxyuridine (BrdU) labeling on acquired resistance to subsequent nephrotoxic insult. Hepatocyte growth factor (HGF)/c-Met axis and other related factors of cell cycle were analyzed. Results: The acquired resistance to rechallenge injury with nephrotoxic dose of UA in rats recovered from mild renal injury was associated with an earlier increase in BrdU-positive PT cells, accelerated upregulation of HGF mRNA, c-Met mRNA/protein, cyclin D1, phospho-Rb and an earlier phenotypic change of PT cells. Colchicine inhibited PT cell proliferation, reduced the upregulated cyclin D1 and phospho-Rb in the kidney, completely abolishing acquired resistance. Conclusions: Cell cycle progression with upregulated renal HGF/c-Met axis may contribute to the accelerated recovery from acute renal failure in rats that recovered from prior mild renal damage, followed by nephrotoxic insult, resulting in partial acquired resistance. Japanese Society of Nephrology, 2011 Acquired resistance nationallicence Acute renal failure nationallicence Apoptosis nationallicence Hepatocyte growth factor nationallicence Proliferation nationallicence Uranyl acetate nationallicence Sun Yuan First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Fujigaki Yoshihide First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Sakakima Masanori First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Fujikura Tomoyuki First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Togawa Akashi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Huang Yanjie First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Hishida Akira First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut Clinical and Experimental Nephrology Springer Japan 15/5(2011-10-01), 666-675 1342-1751 15:5<666 2011 15 10157 https://doi.org/10.1007/s10157-011-0453-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-011-0453-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sun Yuan First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Fujigaki Yoshihide First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Sakakima Masanori First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Fujikura Tomoyuki First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Togawa Akashi First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Huang Yanjie First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Hishida Akira First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, 431-3192, Hamamatsu, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/5(2011-10-01), 666-675 1342-1751 15:5<666 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer