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Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3

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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.

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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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Authors and Affiliations

  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 Biotechnology, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, Korea

    Jong-Min Lee, Dong-Joon Lee & Han-Sung Jung

  2. Departments of Biochemistry, College of Medicine, Institute of Tumor Research, Chungbuk National University, Cheongju-si, Korea

    Suk-Chul Bae

  3. Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China

    Han-Sung Jung

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  1. Jong-Min Lee
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  2. Dong-Joon Lee
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  4. Han-Sung Jung
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Correspondence to Jong-Min Lee or Han-Sung Jung.

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J.-M. Lee and H.-S. Jung have contributed equally as corresponding authors.

J.-M. Lee and D.-J. Lee have contributed equally as first authors.

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Lee, JM., Lee, DJ., Bae, SC. et al. Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3. Histochem Cell Biol 139, 751–758 (2013). https://doi.org/10.1007/s00418-013-1077-x

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