Pdgfd, platelet-derived growth factor D, is a key factor involved in multiple biological processes. It has been associated with regulating stem cell endothelial commitment, with PDGFD genetic deletion or knockdown inhibiting embryonic stem cell (ESC) differentiation into the endothelial cell (EC) lineage and increasing ESC self-renewal, while its overexpression activates ESC differentiation towards ECs via the MAPK/ERK pathway [2]. It also plays a role in the PDGF signaling pathway, which is relevant in various physiological and pathological conditions [1].

In osteosarcoma, single-cell RNA sequencing analysis showed that the PDGF signaling pathway was activated in the primary lesion of non-metastatic osteosarcoma, and PDGFD had an inhibitory effect on osteosarcoma metastasis, likely through suppressing the EMT signaling pathway [1]. In a male atherosclerosis mouse model with Pdgfd knockdown in the SMC lineage, Pdgfd promoted the expansion, migration, and transition of SMC lineage cells to the chondromyocyte phenotype, and increased adventitial fibroblast and pericyte expression of chemokines and leukocyte adhesion molecules, although it had no effect on overall plaque burden [3,4].

In summary, Pdgfd is essential for stem cell endothelial commitment and is involved in the PDGF signaling pathway. Its role in diseases such as osteosarcoma and coronary artery disease has been revealed through functional studies including gene knockdown in mouse models. These findings contribute to understanding the biological functions of Pdgfd and its potential as a therapeutic target in related diseases.

References:

1. Huang, Yujing, Cao, Dongyan, Zhang, Manxue, Min, Daliu, He, Aina. 2024. Exploring the impact of PDGFD in osteosarcoma metastasis through single-cell sequencing analysis. In Cellular oncology (Dordrecht, Netherlands), 47, 1715-1733. doi:10.1007/s13402-024-00949-3. https://pubmed.ncbi.nlm.nih.gov/38652223/

2. Lu, Weisi, Xu, Peipei, Deng, Boxiong, Jiang, Qin, Li, Xuri. 2022. PDGFD switches on stem cell endothelial commitment. In Angiogenesis, 25, 517-533. doi:10.1007/s10456-022-09847-4. https://pubmed.ncbi.nlm.nih.gov/35859222/

3. Kim, Hyun-Jung, Cheng, Paul, Travisano, Stanislao, Jackson, Simon, Quertermous, Thomas. 2023. Molecular mechanisms of coronary artery disease risk at the PDGFD locus. In Nature communications, 14, 847. doi:10.1038/s41467-023-36518-9. https://pubmed.ncbi.nlm.nih.gov/36792607/

4. Kim, Hyun-Jung, Cheng, Paul, Travisano, Stanislao, Jackson, Simon, Quertermous, Thomas. 2023. Molecular mechanisms of coronary artery disease risk at the PDGFD locus. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.26.525789. https://pubmed.ncbi.nlm.nih.gov/36747745/