Regulation of liver regeneration by bone morphogenetic proteins (BMPs) in zebrafish / BMP 訊息分子調控斑馬魚肝臟的再生作用

碩士 / 慈濟大學 / 分子生物暨人類遺傳學系碩士班 / 100 / Several signaling pathways have been reported to play key roles during
liver regeneration after partial hepatectomy (PH). In this study, we focus
on bone morphogenetic protein (Bmp) and fibroblast growth factor (Fgf)
sinaging pathways. Two different PH models, 1/12PH (1/4 of ventral lobe
was removed) and 1/3PH (whole ventral lobe was removed), were established
using the Tg(lfabp:egfp) zebrafish with liver- specific expression of GFP.
Using 1/12PH, a local growth of liver tissue was observed after 5 days
morphologically. Using 1/3PH, incised liver lobe did not regrow but
compensatory growth of the other two dorsal lobes was detected by PCNA
immunochemical staining after 3 days. We used the Tg(hsp:noggin3) fish
for liver regeneration. When heat shock (HS) was performed after 1/12PH
for 5 days, the local liver growth was inhibited, compared to the non-HS
and WT fish. Furthermore, PCNA signal was reduced in Tg(hsp:noggin3) fish
after HS. We also used Tg(hsp70:bmp2b) fish which expressed Bmp2b after
HS for liver regeneration. However, we could not detect the different
local growth between WT and transgenic fish at 5 days after HS in 1/12PH.
Similar approach was applied to Tg(lfabp:dnfgfr1) fish with expression
of dominant negative (dn) Fgfr1 to inhibite Fgf signaling in liver, and
regenerative defect was detected.
We analyzed the expression of proliferation markers (cyclinD, cyclinE,
cdk2, pcna and uhrf1), regenerative genes (plk1, hsp60 and gremlin) and
Bmp–related genes (bmp2a, bmp2b, bmpr1aa, bmpr1bb and noggin3) by
RT-PCR/QRT-PCR in WT fish at 3 days after 1/3PH. Expression of these genes
were greatly changed, especially for bmp2b and bmpr1aa. Expression of
Fgf-related genes (fgfr2c, fgf2, sprouty2, pea3, erm) were also increased.
Importantly, the increased expression of proliferation markers,
regenerative genes, Bmp-related genes and Fgf-related genes were impaired
in Tg(hsp:noggin3) fish after HS. To sum up, these results highly suggest
that Bmp signaling has critical roles in liver regeneration of zebrafish.
Besides that, Bmp signaling may act at upstream of Fgf pathway for the
process.

Identiferoai:union.ndltd.org:TW/100TCU05498008
Date January 2012
CreatorsMeng-Che Chang, 張孟哲
ContributorsWen-Pin Wang, 王文柄
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format64

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