BACKGROUND: Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We investigated whether exogenous application of T3 improves liver regeneration after 70% partial hepatectomy (PH) and confers a survival advantage after 90% subtotal hepatectomy (SH) in rats and whether this is associated with the stimulation of angiogenesis. METHODS: Rats were subjected to PH or SH 10 days after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic proliferation (Ki-67), biochemical markers as well as vascular endothelial growth factor (VEGF) expression were assessed by immunohistochemistry. Gene expression of pathogenic relevant genes was determined by customized cDNA arrays and quantitative RT-PCR. RESULTS: T3-treated rats showed an increased LBR and Ki-67 index after PH and SH, which reached statistical significance compared to placebo-treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an increased expression of VEGF as demonstrated by immunohistochemistry, which was associated with a higher expression of its receptor Flt-1. CONCLUSIONS: Exogenous administration of T3 ameliorates liver regeneration after 70% PH and 90% SH, possibly due to stimulation of angiogenesis. Therefore, its clinical use might be of interest due to its excellent general practicability.
BACKGROUND:Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We investigated whether exogenous application of T3 improves liver regeneration after 70% partial hepatectomy (PH) and confers a survival advantage after 90% subtotal hepatectomy (SH) in rats and whether this is associated with the stimulation of angiogenesis. METHODS:Rats were subjected to PH or SH 10 days after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic proliferation (Ki-67), biochemical markers as well as vascular endothelial growth factor (VEGF) expression were assessed by immunohistochemistry. Gene expression of pathogenic relevant genes was determined by customized cDNA arrays and quantitative RT-PCR. RESULTS:T3-treated rats showed an increased LBR and Ki-67 index after PH and SH, which reached statistical significance compared to placebo-treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an increased expression of VEGF as demonstrated by immunohistochemistry, which was associated with a higher expression of its receptor Flt-1. CONCLUSIONS: Exogenous administration of T3 ameliorates liver regeneration after 70% PH and 90% SH, possibly due to stimulation of angiogenesis. Therefore, its clinical use might be of interest due to its excellent general practicability.
Authors: Marta Szydlowska; Monica Pibiri; Andrea Perra; Elisabetta Puliga; Sandra Mattu; Giovanna M Ledda-Columbano; Amedeo Columbano; Vera P Leoni Journal: Gene Expr Date: 2017-04-13
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