TY - JOUR
T1 - Gene expression profiling reveals multiple protective influences of the peptide α-melanocyte-stimulating hormone in experimental heart transplantation
AU - Colombo, Gualtiero
AU - Gatti, Stefano
AU - Turcatti, Flavia
AU - Sordi, Andrea
AU - Fassati, Luigi R.
AU - Bonino, Ferruccio
AU - Lipton, James M.
AU - Catania, Anna
PY - 2005/9/1
Y1 - 2005/9/1
N2 - Novel therapies are sought to increase efficiency and survival of transplanted organs. Previous research on experimental heart transplantation showed that treatment with the anti-inflammatory peptide α-melanocyte- stimulating hormone (α-MSH) prolongs allograft survival. The aim of the present research was to determine the molecular mechanism of this protective activity. Gene expression profile was examined in heart grafts removed on postoperative days 1 and 4 from rats treated with saline or the synthetic α-MSH analog Nle4DPhe7 (NDP)-α-MSH. On postoperative day 1, the peptide induced expression of cytoskeleton proteins, intracellular kinases, transcription regulators, metallopeptidases, and protease inhibitors. Conversely, NDP-α-MSH repressed immune, inflammatory, cell cycle, and protein turnover mediators. Later effects of α-MSH treatment included down-regulation of oxidative stress response and up-regulation of ion channels, calcium regulation proteins, phosphatidylinositol signaling system, and glycolipidic metabolism. NDP-α-MSH exerted its effects on both Ag-dependent and -independent injury. The results indicate that NDP-α-MSH preserves heart function through a broad effect on multiple pathways and suggest that the peptide could improve the outcome of organ transplantation in combination with immunosuppressive treatments.
AB - Novel therapies are sought to increase efficiency and survival of transplanted organs. Previous research on experimental heart transplantation showed that treatment with the anti-inflammatory peptide α-melanocyte- stimulating hormone (α-MSH) prolongs allograft survival. The aim of the present research was to determine the molecular mechanism of this protective activity. Gene expression profile was examined in heart grafts removed on postoperative days 1 and 4 from rats treated with saline or the synthetic α-MSH analog Nle4DPhe7 (NDP)-α-MSH. On postoperative day 1, the peptide induced expression of cytoskeleton proteins, intracellular kinases, transcription regulators, metallopeptidases, and protease inhibitors. Conversely, NDP-α-MSH repressed immune, inflammatory, cell cycle, and protein turnover mediators. Later effects of α-MSH treatment included down-regulation of oxidative stress response and up-regulation of ion channels, calcium regulation proteins, phosphatidylinositol signaling system, and glycolipidic metabolism. NDP-α-MSH exerted its effects on both Ag-dependent and -independent injury. The results indicate that NDP-α-MSH preserves heart function through a broad effect on multiple pathways and suggest that the peptide could improve the outcome of organ transplantation in combination with immunosuppressive treatments.
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M3 - Article
C2 - 16116233
AN - SCOPUS:23844534723
VL - 175
SP - 3391
EP - 3401
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -