Zfp260, also known as PEX1 (phenylephrine-induced complex-1), is a zinc-finger transcription factor. It plays crucial roles in multiple biological processes, being involved in the regulation of stem cell differentiation, cardiac development, and hypertrophy. Associated pathways include PKC-dependent pathways, α1-adrenergic signaling, and endothelin-1 signaling. Genetic models are valuable for studying its functions [1,2,3].

In skeletal stem cells, Zfp260 is pivotal for the transition from stem to progenitor stages. Its dysfunction leads to lineage arrest at the progenitor stage, impairing bone repair. It maintains chromatin accessibility and regulates Runx2 expression via super-enhancer complexes [1]. In cardiomyocytes, PEX1 knockdown experiments showed its essentiality for the response to endothelin-1. Overexpression of PEX1 can induce cardiomyocyte hypertrophy in vitro and in vivo, and transgenic mice with inducible PEX1 expression develop cardiac hypertrophy [2]. PEX1 deficiency in mice exposed to doxorubicin led to increased apoptosis, while overexpression alleviated apoptosis, suggesting its role in protecting against doxorubicin-induced cardiotoxicity [4]. In rat models, overexpression of PEX1 led to hypertrophic gene induction and increased fibrosis, while silencing PEX1 inhibited pro-fibrotic genes [5].

In conclusion, Zfp260 is essential for the early stage osteo-lineage commitment of skeletal stem cells and is a key regulator in cardiac development, hypertrophy, and protection against cardiotoxicity. Gene knockout or knockdown models in mice have been instrumental in revealing its functions in bone regeneration and heart-related disease conditions such as cardiac hypertrophy and doxorubicin-induced cardiotoxicity.

References:

1. Weng, Yuteng, Feng, Yanhuizhi, Li, Zeyuan, Wang, Haicheng, Wang, Zuolin. 2024. Zfp260 choreographs the early stage osteo-lineage commitment of skeletal stem cells. In Nature communications, 15, 10186. doi:10.1038/s41467-024-54640-0. https://pubmed.ncbi.nlm.nih.gov/39582024/

2. Komati, Hiba, Maharsy, Wael, Beauregard, Janie, Hayek, Salim, Nemer, Mona. 2010. ZFP260 is an inducer of cardiac hypertrophy and a nuclear mediator of endothelin-1 signaling. In The Journal of biological chemistry, 286, 1508-16. doi:10.1074/jbc.M110.162966. https://pubmed.ncbi.nlm.nih.gov/21051538/

3. Debrus, Sophie, Rahbani, Loulwa, Marttila, Minna, Paradis, Pierre, Nemer, Mona. . The zinc finger-only protein Zfp260 is a novel cardiac regulator and a nuclear effector of alpha1-adrenergic signaling. In Molecular and cellular biology, 25, 8669-82. doi:. https://pubmed.ncbi.nlm.nih.gov/16166646/

4. Li, Wenjuan, Xie, Huilin, Hu, Huang, Huang, Jihong, Chen, Sun. 2022. PEX1 is a mediator of α1-adrenergic signaling attenuating doxorubicin-induced cardiotoxicity. In Journal of biochemical and molecular toxicology, 36, e23196. doi:10.1002/jbt.23196. https://pubmed.ncbi.nlm.nih.gov/35979984/

5. Jurado Acosta, Alicia, Rysä, Jaana, Szabo, Zoltan, Nemer, Mona, Ruskoaho, Heikki. 2016. Transcription factor PEX1 modulates extracellular matrix turnover through regulation of MMP-9 expression. In Cell and tissue research, 367, 369-385. doi:10.1007/s00441-016-2527-2. https://pubmed.ncbi.nlm.nih.gov/27826738/