التفاصيل البيبلوغرافية
| العنوان: |
Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice. |
| المؤلفون: |
Kocabayoglu, Peri, Zhang, David Y., Kojima, Kensuke, Hoshida, Yujin, Friedman, Scott L. |
| المصدر: |
Liver International; Jun2016, Vol. 36 Issue 6, p874-882, 9p, 1 Chart, 4 Graphs |
| مصطلحات موضوعية: |
LIVER cells, PLATELET-derived growth factor, LIVER regeneration, HEPATECTOMY, AMINOTRANSFERASES |
| مستخلص: |
Background & Aims Hepatic stellate cells ( HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of beta platelet-derived growth factor (β- PDGFR), which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal β- PDGFR expression. While the role of β- PDGFR is well established in liver injury, its expression and contribution during liver regeneration are unknown. The aim of this study was to determine whether β- PDGFR is induced during liver regeneration following partial hepatectomy ( pHx), and to define its contribution to the regenerative response. Methods Control mice or animals with HSC-specific β- PDGFR-depletion underwent two-thirds pHx followed by assessment of hepatocyte proliferation and expression of β- PDGFR. RNA-sequencing from whole liver tissue of both groups after pHx was used to uncover pathways regulated by β- PDGFR signalling in HSCs. Results Beta platelet-derived growth factor expression on HSCs was up-regulated within 24 h following pHx in control mice, whereas absence of β- PDGFR blunted the expansion of HSCs. Mice lacking β- PDGFR displayed prolonged increases of transaminase levels within 72 h following pHx. Hepatocyte proliferation was impaired within the first 24 h based on Ki-67 and PCNA expression in β- PDGFR-deficient mice. This was associated with dysregulated growth in the β- PDGFR-deficient mice based on RNAseq with pathway analysis, and real-time quantitative PCR, which demonstrated reduced expression of Hgf, Igfbp1, Mapk and Il-6. Conclusions Beta platelet-derived growth factor is induced in HSCs following surgical pHx and its deletion in HSCs leads to prolonged liver injury. However, there is no significant difference in liver regeneration. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
