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Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3

Authors
 Jong-Min Lee  ;  Dong-Joon Lee  ;  Han-Sung Jung  ;  Suk-Chul Bae 
Citation
 Histochemistry and Cell Biology, Vol.139(5) : 751-758, 2013 
Journal Title
 Histochemistry and Cell Biology 
ISSN
 0948-6143 
Issue Date
2013
Abstract
Runt-related transcription factor 3 (Runx3) is essential for normal mouse development, and Runx3 knock-out (KO) mice (FVB strain), which die within 24 h after birth, show various organ defects, such as lung hyperplasia. For proper early liver development, angiogenesis and liver cell differentiation mechanisms are necessary in mammals. Previous studies have reported that various signaling molecules, such as vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and cluster of differentiation 31 (CD31), are closely related to angiogenesis in the developing liver. Proper expression levels of molecules that induce liver cell differentiation, such as phosphorylated Smad2 (pSmad2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Wilms tumor-1 (WT-1) and CD90 (Thy-1), are necessary for fetal liver development. To confirm the pathogenesis of liver defects caused by the loss of function of Runx3, the localization of proliferating cells was examined in wild-type and Runx3 KO mouse livers at postnatal day 1 (PN1). Specimens were also stained for various liver differentiation markers to confirm the function of Runx3. Moreover, gene expression level was examined by real-time quantitative polymerase chain reaction (RT-qPCR). Our results indicate that VEGF, vWF, CD31, pSmad2, NF-kB, WT-1 and Thy-1 were markedly up-regulated by the loss of Runx3. Therefore, our results indicate that liver development is controlled by Runx3. Clarifying the mechanisms of angiogenesis and liver differentiation might aid in the design of efficient and safe antiangiogenic therapy and gene therapy for liver disorders.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86765
DOI
10.1007/s00418-013-1077-x
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
Yonsei Authors
이동준(Lee, Dong Joon) ; 이종민(Lee, Jong Min) ; 정한성(Jung, Han Sung)
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Full Text
http://link.springer.com/article/10.1007%2Fs00418-013-1077-x
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