PTN

What is PTN protein?

PTN (pleiotrophin) gene is a protein coding gene which situated on the long arm of chromosome 7 at locus 7q33. Pleiotrophin (PTN) also known as heparin-binding brain mitogen (HBBM) or heparin-binding growth factor 8 (HBGF-8) or neurite growth-promoting factor 1 (NEGF1) or heparin affinity regulatory peptide (HARP) or heparin binding growth associated molecule (HB-GAM) is a protein that in humans is encoded by the PTN gene. PTN is an 18 kDa growth factor that has a high affinity for heparin. It is structurally related to midkine and retinoic acid induced heparin-binding protein.

What is the function of PTN protein?

PTN is a secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors. It binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups, thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone. In addition, it may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway.

PTN Related Signaling Pathway

PTN binding PTPRZ1 controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway. Or PTN binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation. It can also bind to Wnt ligands and Notch receptors to activate the Wnt/β-catenin signaling pathway and Notch signaling pathway, respectively. When Notch signaling pathway is activated, it can promote biological processes such as neuronal development, angiogenesis and tumorigenesis.

PTN Related Diseases

PTN is abnormally expressed in a variety of tumors, including breast cancer, lung cancer, and colorectal cancer. PTN plays an important role in the proliferation and differentiation of bone cells, and its abnormal expression is associated with the occurrence of bone metabolism-related diseases such as osteoporosis and bone tumors. It is also associated with inflammatory diseases, neurological diseases and cardiovascular diseases.

Fig1. Graphical summary of the iatrogenic induction of PTN-mediated self-renewal and proliferation in glioblastoma recurrences. (Arnon Møldrup Knudsen, 2022)

Bioapplications of PTN

More commonly, PTN is used as a therapeutic target for related diseases and drug development targets. PTN can be used for the treatment of bone diseases and the repair of fractures. In addition, PTN can promote the reconstruction of neuronal networks by promoting neuronal migration and synaptic formation, so it has been widely studied and applied to nervous system repair and regeneration.

Case study 1: Yayun Zhang, 2023

The refined functional cell subtypes in the immune microenvironment of specific titanium (Ti) surface and their collaborative role in promoting bone marrow mesenchymal stem cells (BMSCs) driven bone integration need to be comprehensively characterized.

This study employed a simplified co-culture system to investigate the dynamic, temporal crosstalk between macrophages and BMSCs on the Ti surface. The M2-like sub-phenotype of macrophages, characterized by secretion of CXCL chemokines, emerges as a crucial mediator for promoting BMSC osteogenic differentiation and bone integration in the Ti surface microenvironment. The secretion of CXCL3, CXCL6, and CXCL14 by M2-like macrophages plays a pivotal role. The process activates CXCR2 and CCR1 receptors, triggering downstream regulatory effects on the actin cytoskeleton pathway within BMSCs, ultimately fostering osteogenic differentiation. PTN maintains the M2-like phenotype via the Sdc3 receptor-mediated cell adhesion molecules pathway.
The findings provide a novel insight into the intricate communication and mutual regulatory mechanisms operating between BMSCs and macrophages on the Ti surface, highlight specific molecular events governing cell-cell interactions in the osteointegration.

Fig1. Protein expression profiles of CXCL3, CXCL6, CXCL14, and PTN over time in separate and co-culture systems.

Fig2. Expression of osteoblast-related genes and corresponding regulatory molecules in BMSCs at various time points with or without si-Pfn2 interference at protein levels.

Case study 2: Arnon Møldrup Knudsen, 2022

Glioblastomas are highly resistant to therapy, and virtually all patients experience tumor recurrence after standard-of-care treatment. Surgical tumor resection is a cornerstone in glioblastoma therapy, but its impact on cellular phenotypes in the local postsurgical microenvironment has yet to be fully elucidated.

The team developed a preclinical orthotopic xenograft tumor resection model in rats with integrated 18F-FET PET/CT imaging. Differentially expressed genes and pathways were investigated and validated using tissue specimens from the xenograft model, 23 patients with matched primary/recurrent tumors, and a cohort including 190 glioblastoma patients. Functional investigations were performed in vitro with multiple patient-derived cell cultures. The human Pleiotrophin/PTN ELISA Kit (Invitrogen) was used according to the manufacturer's instructions.
Recurrent tumors expressed elevated levels of pleiotrophin (PTN), secreted by both tumor cells and tumor-associated microglia/macrophages. Mechanistically, PTN could induce tumor cell proliferation, self-renewal, and the stem cell program. In short, Surgical tumor resection is an iatrogenic driver of PTN-mediated self-renewal in glioblastoma tumor cells that promotes therapeutic resistance and tumor recurrence.

Fig3. Representative immunofluorescence images showing PTN expression in primary vs recurrent P3 xenografts.

Fig4. Exogenous PTN induced proliferation after 5-day treatment of all 4 investigated spheroid cultures .

PTN has several biochemical functions, for example, chondroitin sulfate proteoglycan binding,growth factor activity,heparin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PTN itself. We selected most functions PTN had, and list some proteins which have the same functions with PTN. You can find most of the proteins on our site.

PTN has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PTN here. Most of them are supplied by our site. Hope this information will be useful for your research of PTN.

SGTA;CHD3;TAF1D;UBQLN4;DNAJB11;SMAP;PSMD11;EIF3F;CACNB4;TXNDC9;PLXNB2;SGSM2;NUDT21;DFNA5;PFDN1