Cited by 104Proteoglycans and glycosaminoglycans researchCytokine Signaling Pathways and InteractionsFibroblast Growth Factor Research

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Pleiotrophin: Activity and mechanism

Open access

Xu Wang·2020·Advances in Clinical Chemistry

DOI 10.1016/bs.acc.2020.02.003PMC PMC7672882

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Abstract

Pleiotrophin (PTN) is a potent mitogenic cytokine with a high affinity for the polysaccharide glycosaminoglycan (GAG). Although it is most strongly associated with neural development during embryogenesis and the neonatal period, its expression has also been linked to a plethora of other physiological events including cancer metastasis, angiogenesis, bone development, and inflammation. A considerable amount of research has been carried out to understand the mechanisms by which PTN regulates these events. In particular, PTN has now been shown to bind a diverse collection of receptors including many GAG-containing proteoglycans. These interactions lead to the activation of many intracellular kinases and, ultimately, activation and transformation of cells. Structural studies of PTN in complex with both GAG and domains from its non-proteoglycan receptors reveal a binding mechanism that relies on electrostatic interactions and points to PTN-induced receptor oligomerization as one of the possible ways PTN uses to control cellular functions.

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Additional file 1 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273281
Additional file 5 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273293
Additional file 1 of Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis
Deng, X., Mo, Y., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26715421
Additional file 9 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273305
Additional file 4 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273290
Additional file 5 of Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis
Deng, X., Mo, Y., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26715433
Additional file 4 of Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis
Deng, X., Mo, Y., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26715430
Additional file 10 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273308
Additional file 1 of PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1
Zhao, X., Liu, L., Huang, Z., Zhu, F., Zhang, H., & Zhou, D. (2024) · Figshare · doi:10.6084/m9.figshare.27042441
Additional file 2 of Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis
Deng, X., Mo, Y., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26715424
Additional file 2 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273284
Additional file 3 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273287
Additional file 8 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273302
Additional file 2 of PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1
Zhao, X., Liu, L., Huang, Z., Zhu, F., Zhang, H., & Zhou, D. (2024) · Figshare · doi:10.6084/m9.figshare.27042444
Additional file 7 of Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Lin, C., Chen, Y. K., Zhang, F., Zhu, P., Yu, L., & Chen, W. (2023) · Figshare · doi:10.6084/m9.figshare.23273299
Additional file 3 of Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis
Deng, X., Mo, Y., & Zhu, X. (2024) · Figshare · doi:10.6084/m9.figshare.26715427
Pleiotrophin Promotes Megakaryocyte Differentiation and Thrombocytopoiesis by Regulating PTPRZ1–Fyn–Akt Signaling in Thrombocytopenia after Allo-HSCT
He, W., Qi, J., Wang, P. F., Song, X., Zhang, Z., Gu, C., Jiang, S., Han, P., Ye, B., Wu, D., et al. (2026) · Thrombosis and Haemostasis · doi:10.1055/a-2820-4095
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Evidence of the role of Midkine and Pleiotrophin in the pathogenesis of Familial Mediterranean Fever
Abdallah, Z. Y., Eldeen, G. N., Sokkar, M. F., Abdelkawy, R. F. M., Lotfy, R. S., Hussein, S. H., Hamed, K., & El-Bassyouni, H. T. (2026) · European Journal of Pediatrics · doi:10.1007/s00431-026-06981-9
Pleiotrophin in Mammary Gland Development and Breast Cancer: A Comprehensive Review of the Evidence
GHOLAMI, A. S., Walsh, C. N., & McBryan, J. (2026) · Cells · doi:10.3390/cells15100927
Spatial Analysis Reveals Gene Expression and Microenvironmental Changes in the Transition of Nevus to Melanoma
Kreuger, I. Z. M., Merkus, V. A., de Haan, S., Schrader, A. M. R., Scheeren, F. A., van der Burg, S. H., van Groningen, T., Slieker, R. C., & van Doorn, R. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-2934
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Yang, L., Zhang, J., Chen, Y., Wei, Z.-Q., Zhou, M., Chen, G., He, Y.-X., Huang, Z., Li, S., Tang, K.-Q., et al. (2026) · Future Science OA · doi:10.1080/20565623.2026.2696931
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Short-term, Long-term, and Genetic Determinants of Human Plasma Proteome VariabilityPreprint
Benacom, D., Specht, A., Nicholas, J. C., Guillard, R., Gillman, M. G., Dubin, R. F., Ganz, P., Rotter, J. I., Taylor, K. D., Rich, S. S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.30.741635

Authors: Wang, X.
Affiliations: Arizona State University (US)
Corresponding author: Xu Wang
ORCID: Xu Wang
Venue: Advances in Clinical Chemistry
Publisher: Elsevier
Published: 2020
Volume: 98
Pages: 51-89
ISSN: 0065-2423 (ISSN-L)
DOI: 10.1016/bs.acc.2020.02.003
PMC: PMC7672882
OpenAlex: W3011324370
Cited by: 98
References: 166
Citations by year: 2026: 22 · 2025: 16 · 2024: 26 · 2023: 22 · 2022: 10 · 2021: 2
FWCI: 14.22
Type: book chapter
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Advances in clinical chemistry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM118518)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Keywords: pleiotrophin, glycosaminoglycan binding, proteoglycans, receptor oligomerization, electrostatic interactions, receptor activation, cell transformation, metastasis, angiogenesis, skeletal development, inflammation, neural development, protein structure
MeSH terms: Animals, Carrier Proteins, Cell Differentiation, Humans, Neoplasms, Cytokines

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