Wnt pathway regulation in chronic renal allograft damage
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Wnt pathway regulation in chronic renal allograft damage. / von Toerne, C; Schmidt, C; Adams, J; Kiss, E; Bedke, J; Porubsky, S; Gretz, N; Lindenmeyer, M T; Cohen, C D; Gröne, H-J; Nelson, P J.
in: AM J TRANSPLANT, Jahrgang 9, Nr. 10, 10.2009, S. 2223-39.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Wnt pathway regulation in chronic renal allograft damage
AU - von Toerne, C
AU - Schmidt, C
AU - Adams, J
AU - Kiss, E
AU - Bedke, J
AU - Porubsky, S
AU - Gretz, N
AU - Lindenmeyer, M T
AU - Cohen, C D
AU - Gröne, H-J
AU - Nelson, P J
PY - 2009/10
Y1 - 2009/10
N2 - The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1(lvl)) to Lewis (RT1(l)) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention.
AB - The Wnt signaling pathway, linked to development, has been proposed to be recapitulated during the progressive damage associated with chronic organ failure. Chronic allograft damage following kidney transplantation is characterized by progressive fibrosis and a smoldering inflammatory infiltrate. A modified, Fischer 344 (RT1(lvl)) to Lewis (RT1(l)) rat renal allograft model that reiterates many of the major pathophysiologic processes seen in patients with chronic allograft failure was used to study the progressive disease phenotype and specific gene product expression by immunohistochemistry and transcriptomic profiling. Central components of the Tgfb, canonical Wnt and Wnt-Ca2+ signaling pathways were significantly altered with the development of chronic damage. In the canonical Wnt pathway, Wnt3, Lef1 and Tcf1 showed differential regulation. Target genes Fn1, Cd44, Mmp7 and Nos2 were upregulated and associated with the progression of renal damage. Changes in the Wnt-Ca2+ pathway were evidenced by increased expression of Wnt6, Wnt7a, protein kinase C, Cam Kinase II and Nfat transcription factors and the target gene vimentin. No evidence for alterations in the Wnt planar cell polarity (PCP) pathway was detected. Overall results suggest cross talk between the Wnt and Tgfb signaling pathways during allograft inflammatory damage and present potential targets for therapeutic intervention.
KW - Animals
KW - Cell Differentiation
KW - Cell Polarity
KW - Fibrosis
KW - Gene Expression Profiling
KW - Immunohistochemistry
KW - Kidney
KW - Kidney Transplantation
KW - Male
KW - Models, Animal
KW - Polymerase Chain Reaction
KW - RNA, Messenger
KW - Rats
KW - Rats, Inbred F344
KW - Rats, Inbred Lew
KW - Signal Transduction
KW - Transplantation, Homologous
KW - Wnt Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1111/j.1600-6143.2009.02762.x
DO - 10.1111/j.1600-6143.2009.02762.x
M3 - SCORING: Journal article
C2 - 19681821
VL - 9
SP - 2223
EP - 2239
JO - AM J TRANSPLANT
JF - AM J TRANSPLANT
SN - 1600-6135
IS - 10
ER -