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Histochemistry and Cell Biology

, Volume 139, Issue 5, pp 751–758 | Cite as

Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3

  • Jong-Min LeeEmail author
  • Dong-Joon Lee
  • Suk-Chul Bae
  • Han-Sung JungEmail author
Short Communication

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.

Keywords

Runx3 KO Liver Differentiation Angiogenesis 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. NRF 2012-0002688).

We are thankful to Dr. Jeong-Oh Shin for providing RT-qPCR data.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Division in Anatomy and Developmental Biology, Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of BiotechnologyYonsei UniversitySeoulKorea
  2. 2.Departments of Biochemistry, College of Medicine, Institute of Tumor ResearchChungbuk National UniversityCheongju-siKorea
  3. 3.Oral Biosciences, Faculty of DentistryThe University of Hong KongHong Kong SARChina

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