We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.
Fibrosis, closely related to chronic various diseases, is a pathological process characterised by the accumulation of collagen (largely collagen type I). Non-invasive methods are necessary for the diagnosis and follow-up of fibrosis. This study aimed to develop a collagen-targeted probe for the molecular imaging of fibrosis. We identified CPKESCNLFVLKD (CBP1495) as an original collagen-binding peptide using isothermal titration calorimetry and enzyme-linked immunosorbent assay. CBP1495 effectively bound to collagen type I (K = 861 nM) and (GPO) (K = 633 nM), a collagen mimetic peptide. Western blot and histochemistry validated CBP1495 targeting collagen in vitro and ex vivo. (Gly-(D)-Ala-Gly-Gly) was introduced to CBP1495 for couplingTc. Labelling efficiency of Tc-CBP1495 was 95.06 ± 1.08 %. The physico-chemical properties, tracer kinetics and biodistribution ofTc-CBP1495 were carried out, and showed that the peptide stably chelated Tc in vitro and in vivo. SPECT/CT imaging withTc-CBP1495 was performed in rat fibrosis models, and revealed that Tc-CBP1495 significantly accumulated in fibrotic lungs or livers of rats. Finally,Tc-CBP1495 uptake and hydroxyproline (Hyp), a specific amino acid of collagen, were quantitatively analysed. The results demonstrated that Tc-CBP1495 uptake was positvely correlated with Hyp content in lungs (P< 0.0001, r = 0.8266) or livers (P< 0.0001, r = 0.7581). Therefore, CBP1495 is a novel collagen-binding peptide, andTc-labelled CBP1495 may be a promising radiotracer for the molecular imaging of fibrosis.
The aim is to clarify expression changes of ERK1/2, STAT3 and SHP-2 in bone marrow cells from gamma-ray induced leukemia mice. A mouse model of gamma-ray induced leukemia was produced, and by means of quantitative real-time PCR, immunoprecipitation, Western blotting and electrophoretic mobility shift assays (EMSA), the expression of mRNA and protein, phosphorylation level, and protein activity of ERK1/2, STAT3 and SHP-2 in bone marrow cells were investigated in these mice. The results indicated that mRNA and protein expressions of ERK1/2 were upregulated, with significant increase of phosphorylation level and protein activity, but with insignificant differences in mRNA and protein expressions, phosphorylation level and protein activity of STAT3 and SHP-2 in bone marrow cells from gamma-ray induced leukemia mice compared to the radiation/tumor-free or control mice. It is concluded that in the pathogenesis of gamma-ray induced leukemia in Balb/C mice, activated ERK1/2 pathway may play a role, without involving STAT3 pathway; meanwhile, SHP-2 exerts no regulative effect on pathways of Ras-ERK1/2 and JAK-STAT.
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