Pleiotrophin (PTN), belonging to the subfamily of heparin-binding growth factors, has diverse functions. It binds to receptors like Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, anaplastic lymphoma kinase (ALK), and others, regulating various signaling pathways such as AKT and MAPK. PTN is involved in multiple biological processes including inflammation, angiogenesis, oncogenesis, and tissue regeneration, making it of great biological importance [1].

Mice lacking PTN exhibit impaired adult hippocampal neurogenesis (AHN) accompanied by poor learning and memory, indicating PTN's role in maintaining normal AHN and cognitive function [2]. In the context of cancer, siRNA-mediated PTN knockdown in epithelial ovarian cancer cells induced apoptotic cell death, suggesting its significance in ovarian cancer pathogenesis [4]. Also, in hepatitis B virus-related cirrhosis-HCC progression, PTN may act as a mediator from cancer-associated fibroblasts to promote tumor cell proliferation [3].

In conclusion, PTN is crucial for functions like AHN and cognitive function, and is significantly involved in diseases such as neurodegenerative disorders, ovarian cancer, and hepatitis B-related liver diseases. Studies using PTN knockout mouse models have been instrumental in revealing its role in these biological processes and disease conditions, providing potential therapeutic targets for related diseases.

References:

1. Xu, Chuanying, Zhu, Shunying, Wu, Mingyuan, Han, Wei, Yu, Yan. . Functional receptors and intracellular signal pathways of midkine (MK) and pleiotrophin (PTN). In Biological & pharmaceutical bulletin, 37, 511-20. doi:. https://pubmed.ncbi.nlm.nih.gov/24694599/

2. Li, Haoyang, Xu, Li, Jiang, Wei, Cui, Yaxiong, Tang, Changyong. 2023. Pleiotrophin ameliorates age-induced adult hippocampal neurogenesis decline and cognitive dysfunction. In Cell reports, 42, 113022. doi:10.1016/j.celrep.2023.113022. https://pubmed.ncbi.nlm.nih.gov/37610873/

3. Lin, Chenhong, Chen, Yeda, Zhang, Feng, Yu, Liangliang, Chen, Wenbiao. 2023. Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression. In Gut pathogens, 15, 26. doi:10.1186/s13099-023-00554-z. https://pubmed.ncbi.nlm.nih.gov/37259127/

4. Sethi, Geetika, Kwon, Youngjoo, Burkhalter, Rebecca J, Tawfik, Ossama W, Godwin, Andrew K. 2014. PTN signaling: Components and mechanistic insights in human ovarian cancer. In Molecular carcinogenesis, 54, 1772-85. doi:10.1002/mc.22249. https://pubmed.ncbi.nlm.nih.gov/25418856/