TY - JOUR
T1 - Early activation of fibrogenesis in transplanted kidneys: a study on serial renal biopsies.
AU - Del Prete, Dorella
AU - Ceol, Monica
AU - Anglani, Franca
AU - Vianello, Daniela
AU - Tiralongo, Emilia
AU - Valente, Marialuisa
AU - Graziotto, Romina
AU - Bonfante, Luciana
AU - Scaparrotta, Giuseppe
AU - Furian, Lucrezia
AU - Rigotti, Paolo
AU - Gambaro, Giovanni
AU - D'Angelo, Angela
PY - 2009
Y1 - 2009
N2 - BACKGROUND/AIMS: In kidney transplants, the renin-angiotensin system (RAS) is involved in systemic and local changes that may induce fibrosis. Our aim was to use gene expression and immunohistochemical analysis to investigate the RAS and several factors involved in the fibrogenic cascade in allograft biopsies.
METHODS: We considered 43 donor biopsies (T0), 18 biopsies obtained for diagnostic purposes (Td) and 24 protocol biopsies (Tp) taken 2 months after transplantation in patients with stable renal function. Morphometric alpha SMA and TGF beta 1 analysis, and Masson's Trichrome staining were performed. mRNA levels of angiotensinogen, renin, ACE, AT1-R, AT2-R, TGF beta 1, BMP-7, Coll III, fibronectin and alpha SMA were analyzed by real-time RT/PCR. MDRD a year after the transplant was also considered.
RESULTS: Significantly higher levels of AT1-R and alpha SMA transcripts were found in Tp than in T0. Regression analysis showed significant TGF beta 1-independent positive correlations between RAS and matrix components in T0 and Tp, but more evident in Tp, where a positive correlation between TGF beta 1 and Masson's Trichrome stained areas was also seen.
CONCLUSION: Our results suggest that RAS and TGF beta 1-related fibrogenic loops are activated as early as 2 months after kidney transplantation.
AB - BACKGROUND/AIMS: In kidney transplants, the renin-angiotensin system (RAS) is involved in systemic and local changes that may induce fibrosis. Our aim was to use gene expression and immunohistochemical analysis to investigate the RAS and several factors involved in the fibrogenic cascade in allograft biopsies.
METHODS: We considered 43 donor biopsies (T0), 18 biopsies obtained for diagnostic purposes (Td) and 24 protocol biopsies (Tp) taken 2 months after transplantation in patients with stable renal function. Morphometric alpha SMA and TGF beta 1 analysis, and Masson's Trichrome staining were performed. mRNA levels of angiotensinogen, renin, ACE, AT1-R, AT2-R, TGF beta 1, BMP-7, Coll III, fibronectin and alpha SMA were analyzed by real-time RT/PCR. MDRD a year after the transplant was also considered.
RESULTS: Significantly higher levels of AT1-R and alpha SMA transcripts were found in Tp than in T0. Regression analysis showed significant TGF beta 1-independent positive correlations between RAS and matrix components in T0 and Tp, but more evident in Tp, where a positive correlation between TGF beta 1 and Masson's Trichrome stained areas was also seen.
CONCLUSION: Our results suggest that RAS and TGF beta 1-related fibrogenic loops are activated as early as 2 months after kidney transplantation.
KW - fibrogenesis
KW - kidney
KW - transplantation
KW - fibrogenesis
KW - kidney
KW - transplantation
UR - http://hdl.handle.net/10807/10285
U2 - 10.1016/j.yexmp.2009.07.004
DO - 10.1016/j.yexmp.2009.07.004
M3 - Article
SN - 0014-4800
VL - 87
SP - 141
EP - 145
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
ER -