Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver Sinusoidal Endothelial Cell Dedifferentiation
Open accessAbstract
Sinusoidal dedifferentiation is a complicated process induced by several factors, and exists in early stage of diverse liver diseases. The mechanism of sinusoidal dedifferentiation is poorly unknown. In this study, we established a NaAsO 2-induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial cells were isolated and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic approach was adopted to globally examine the effects of arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of sinusoidal dedifferentiation. In all, 4205 proteins were identified and quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were significantly changed in NaAsO 2 group, compared with the normal control. Validation by western blot showed increased level of clathrin-associated sorting protein Disabled 2 (Dab2) in NaAsO 2 group, indicating that it may regulate receptor endocytosis, which served as a mechanism to augment intracellular VEGF signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and angiogenesis.
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The early HSEC transcriptome suggests the activation of sinusoidal function, including endocytosis, antigen presentation, and signaling.
“the early HSEC transcriptome further suggests the activation of sinusoidal function, including endocytosis (Stab2, Colec12, Ehd3, and Lyve1), antigen presentation (Fcgrt, Fcer1g, and Mrc1), and signaling (Gpr182, Bmp2, Dll4, and Efna1)”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Lao et al., 2017
The Results (Bioinformatic analysis; Experimental Validation; pages unavailable) report increased endocytosis-related proteins during LSEC dedifferentiation, but decreased proteins related to innate immune response and antigen presentation. The paper analyzes a proteome, not an early HSEC transcriptome, and does not support the listed genes or a combined activation of all three functions. (LLM, conf=0.86)
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Jung, J., Jin, M., Park, N., 최한이, & Na, K. (2026) · Acta Biomaterialia · doi:10.1016/j.actbio.2026.06.032
- Authors
- Lao, Y., Li, Y., Hou, Y., Chen, H., Qiu, B., Lin, W., Sun, A., Wei, H., Jiang, Y., & He, F.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Tsinghua University (CN)
- Beijing Proteome Research Center (CN)
- Corresponding author
- Jiang, Ying
- He, Fuchu
- Venue
- Scientific Reports
- Published
- 2017-10-18
- Volume
- 7
- Issue
- 1
- Pages
- 13456-13456
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5647404
- OpenAlex
- W2762636597
- Cited by
- 5
- References
- 37
- Citations by year
- 2026: 1 · 2022: 2 · 2020: 1 · 2019: 1
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (SQ2017YFSF090210, 973 Program, 2013CB910502, 81123001, 81570526, 16CXZ027)
- Tsinghua University
- National Key Research and Development Program of China (2013 CB910502, 16CXZ027, SQ2017YFSF090210, 2014CBA02001, 2016YFC0902400)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- liver sinusoidal endothelial cells, Dab2, receptor internalization, arsenic, VEGF signaling, angiogenesis, proteomic profiling, liver disease
- MeSH terms
- Animals, Cell Separation, Endocytosis, Liver, Male, Receptors, Cell Surface, Reproducibility of Results, Immunomagnetic Separation, Computational Biology, Proteome, Adaptor Proteins, Vesicular Transport, Proteomics, Endothelial Cells, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice, Cell Dedifferentiation
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