| Title: |
Experimental models of CKD |
| Authors: |
Kanlaya, Rattiyaporn; Sintiprungrat, Kitisak; Thongboonkerd, Visith; Torremadé, Noelia; Bindels, René; Hoenderop, Joost; Fernandez, Elvira; Dusso, Adriana; Valdivielso, Jose M.; Krueger, Thilo; Boor, Peter; Schafer, Cora; Westenfeld, Ralf; Brandenburg, Vincent; Schlieper, Georg; Jahnen-Dechent, Willi; Ketteler, Markus; Jee, Webster; Li, Xiaodong; Richards, Bill; Floege, Jürgen; Gonçalves, Janaína G.; Canale, Daniele; de Bragança, Ana Carolina; Shimizu, Maria Heloisa M.; Moyses, Rosa Maria A.; Andrade, Lucia; Seguro, Antonio C.; Volpini, Rildo A.; Romoli, Simone; Migliorini, Adriana; Anders, Hans-Joachim; Eskova, Olga; Neprintseva, Natalia; Tchebotareva, Natalia; Bobkova, Irina; Kozlovskaya, Lidiya; Simic, Ivana; Tabatabaeifar, Mansoureh; Wlodkowski, Tanja; Denc, Helga; Mollet, Geraldine; Antignac, Corinne; Schaefer, Franz; Ekaterina, Ivanova A.; Giardino, Laura; Rastaldi, Maria Pia; Van den Heuvel, Lambertus; Levtchenko, Elena; Okina, Chikako; Okamoto, Tomoko; Kamata, Mariko; Murano, Junya; Kobayashi, Kei; Takeuchi, Kazuhiro; Kamata, Fumi; Sakai, Takeshi; Naito, Shokichi; Aoyama, Togo; Sano, Takashi; Takeuchi, Yasuo; Kamata, Kouju; Thomasova, Dana; Bruns, Hauke A.; Liapis, Helen; Iwashita, Takatsugu; Hasegawa, Hajime; Takayanagi, Kaori; Shimizu, Taisuke; Asakura, Juko; Okazaki, Shinpei; Kogure, Yuta; Hatano, Minoru; Hara, Hiroaki; Inamura, Megumi; Iwanaga, Mizuki; Mitani, Tomoyuki; Mitarai, Tetsuya; Savin, Virginia J.; Sharma, Mukut; Wei, Changli; Reiser, Jochen; McCarthy, Ellen T.; Sharma, Ram; Gauchat, Jean-Francois; Eneman, Benedicte; Freson, Kathleen; Van Geet, Chris; Choi, Dae Eun; Jeong, Jin Young; Chang, Yoon Kyung; Na, Ki-Ryang; Lee, Kang Wook; Shin, Young Tai; Ni, Hai-Feng; Chen, Jun-Feng; Zhang, Ming-Hui; Pan, Ming-Ming; Liu, Bi-Cheng; Kim, Seong Suk; Suzuki, Taihei; Iyoda, Masayuki; Matsumoto, Kei; Shindo-Hirai, Yuki; Kuno, Yoshihiro; Wada, Yukihiro; Yamamoto, Yasutaka; Shibata, Takanori; Akizawa, Tadao; Muñoz-Felix, Jose M.; Lopez-Novoa, Jose M.; Martinez-Salgado, Carlos; Ehling, Josef; Bábícková, Janka; Gremse, Felix; Kiessling, Fabian; Lammers, Twan; Lech, Maciej; Günthner, Roman; Lorenz, Georg; Ryu, Mi; Gröbmayr, Regina; Susanti, Heni; Kobayashi, Koichi S.; Flavell, Richard A.; Rayego-Mateos, Sandra; Morgado, Jose; Sanz, Ana Belen; Eguchi, Satoru; Pato, Janos; Keri, Gyorgy; Egido, Jesus; Ortiz, Alberto; Ruiz-Ortega, Marta; Leduc, Martin; Geerts, Lilianne; Grouix, Brigitte; Sarra-Bournet, François; Felton, Alexandra; Gervais, Liette; Abbott, Shaun; Duceppe, Jean-Simon; Zacharie, Boulos; Penney, Christopher; Laurin, Pierre; Gagnon, Lyne; Detsika, Maria G.; Duann, Pu; Lianos, Elias A.; Leong, Ka Ian; Chiang, Chih-Kang; Yang, Ching-Chin; Wu, Cheng-Tien; Chen, Li-Ping; Hung, Kuan-Yu; Liu, Shing-Hwa; Carvalho, Fernando F.; Teixeira, Vicente P.; Almeida, Waldemar S.; Schor, Nestor; Small, David M.; Bennett, Nigel C.; Coombes, Jeff; Johnson, David W.; Gobe, Glenda C.; Montero, Nuria; Prada, Alejandra; Riera, Marta; Orfila, María; Pascual, Julio; Rodríguez, Eva; Barrios, Clara; Kokeny, Gabor; Fazekas, Krisztina; Rosivall, Laszlo; Mozes, Miklos M.; Hornigold, Nick; Hughes, Jeremy; Mooney, Andrew; Benardeau, Agnes; Riboulet, William; Vandjour, Anthony; Jacobsen, Bjoern; Apfel, Christian; Conde-Knape, Karin; Bienvenu, Jean-François; Tanaka, Tetsuhiro; Yamaguchi, Junna; Nangaku, Masaomi; Niwa, Toshimitsu; Bolati, Dilinaer; Shimizu, Hidehisa; Yisireyili, Maimaiti; Nishijima, Fuyuhiko; Brocca, A.; Virzì, G.; de Cal, M.; Ronco, C.; Priante, Giovanna; Musacchio, Estella; Valvason, Chiara; Sartori, Leonardo; Piccoli, Antonio; Baggio, Bruno; Perkuhn, Michael; Weibrecht, Martin; Zok, Stephanie; Martin, Ina V.; Schoth, Felix; Ostendorf, Tammo; Kuhl, Christiane; Karabaeva, Aigul; Essaian, Ashot; Beresneva, Olga; Parastaeva, Marina; Kayukov, Ivan; Smirnov, Alexey; Audzeyenka, Irena; Kasztan, Malgorzata; Piwkowska, Agnieszka; Rogacka, Dorota; Angielski, Stefan; Jankowski, Maciej; Bockmeyer, Clemens L.; Kokowicz, Karen; Agustian, Putri A.; Zell, Stephanie; Wittig, Juliane; Becker, Jan U.; Nishizono, Ryuzoh; Venkatareddy, Madhusudan P.; Chowdhury, Marboob A.; Wang, Su Q.; Fukuda, Akihiro; Wickman, Larysa T.; Yang, Yan; Wiggins, Roger C.; Fazio, Maria Rosaria; Donato, Valentina; Lucisano, Silvia; Cernaro, Valeria; Lupica, Rosaria; Trimboli, Domenico; Montalto, Gaetano; Aloisi, Carmela; Mazzeo, Anna Teresa; Buemi, Michele; Gawrys, Olga; Olszynski, Krzysztof H.; Kuczeriszka, Marta; Gawarecka, Katarzyna; Swiezewska, Ewa; Chmielewski, Marek; Masnyk, Marek; Rafalowska, Janina; Kompanowska-Jezierska, Elzbieta; Lee, Wen-Chin; Chau, You-Ying; Lee, Lung-Chih; Chiu, Chien-Hua; Lee, Chien-Te; Chen, Jin-Bor; Kim, Woo-Kyung; Shin, Sung Joon |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2013 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Abstracts |
| Description: |
Introduction and Aims: Kidney stone disease is associated with renal fibrosis by the unclear mechanisms. We hypothesized that calcium oxalate (CaOx), a major crystalline component of kidney stones, could induce secretion of fibrotic factors from macrophages leading to “ epithelial mesenchymal transition/transdifferentiation ” (EMT) of renal tubular cells. Methods: EMT markers were examined by Western blot analysis and immunofluorescence study. Level of TGF-β1 in the “ secreted products of CaOx-exposed macrophages ” (CaOx-M-Sup) and cellular levels of the cascade signaling molecule RhoA as well as the ubiquitinated proteins were measured. Finally, a proteasome inhibitor (MG132) was applied to examine whether the intervention of ubiquitin-proteasome pathway (UPP) could prevent EMT and changes in RhoA induced by CaOx-M-Sup. Results: Western blot analysis revealed an increased level of vimentin (mesenchymal marker) but decreased levels of E-cadherin and cytokeratin (epithelial markers) in MDCK cells treated with CaOx-M-Sup. Immunofluorescence study confirmed the increased level of vimentin and decreased level of cytokeratin, and also revealed the increased level of fibronectin (another mesenchymal marker). The data also showed decreased levels and disorganization of F-actin (cytoskeletal marker) and zonula occludens-1 (ZO-1) (tight junction marker) induced by CaOx-M-Sup. ELISA demonstrated the increased level of transforming growth factor-β1 (TGF-β1), the well-defined EMT inducer, in CaOx-M-Sup. Downstream signaling of TGF-β1 was involved as demonstrated by the decreased level of RhoA. Interestingly, pretreatment with MG132 could restore RhoA to its basal level, most likely through UPP. Moreover, MG132 successfully sustained cytoskeletal assembly and tight junction, and could prevent the cells from EMT. Conclusions: Altogether, these data demonstrate for the first time that CaOx-M-Sup could induce EMT in renal tubular cells by TGF-β1 signaling cascade via RhoA and UPP. This may be, at least in part, the underlying ... |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://ndt.oxfordjournals.org/cgi/content/short/28/suppl_1/i185; http://dx.doi.org/10.1093/ndt/gft114 |
| DOI: |
10.1093/ndt/gft114 |
| Availability: |
http://ndt.oxfordjournals.org/cgi/content/short/28/suppl_1/i185; https://doi.org/10.1093/ndt/gft114 |
| Rights: |
Copyright (C) 2013, European Renal Association - European Dialysis and Transplant Association |
| Accession Number: |
edsbas.D7F71581 |
| Database: |
BASE |