Fgf7-KO Mouse

Fgf7, also known as keratinocyte growth factor, is a member of the fibroblast growth factor (FGF) family. It plays a crucial role in numerous biological processes such as organ development, cell proliferation, and tissue repair. Specifically, Fgf7 is secreted by mesenchyme and activates the "b" isoforms of FGFR1 and FGFR2 in the epithelium, contributing to the development of organs, glands, and limbs [2].

Single-cell RNA-seq analysis has revealed that Fgf7 mediates a novel interaction between muscle fibro-adipogenic progenitors (FAPs) and satellite cells. Exogenous FGF7 can augment satellite cell proliferation, which benefits muscle regeneration and counteracts age-related myopathy [1]. In the context of COVID-19, FGF7 enhances the expression of ACE2 in human islet organoids, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion [3]. In rhabdomyosarcomas, an FGF7-FGFR2 autocrine loop increases tumor growth and chemoresistance [4]. In ovarian cancer, cancer-associated fibroblast-secreted FGF7 promotes cancer progression by inhibiting the ubiquitination and degradation of HIF-1α [5].

In conclusion, Fgf7 is essential for multiple biological functions, especially in cell-cell communication and tissue development. Its dysregulation is implicated in various diseases, including muscle-related disorders, COVID-19-associated diabetes, and different types of cancers. Research on Fgf7 using relevant models helps to understand the underlying mechanisms of these diseases, potentially providing new therapeutic targets.

References:

1. Ma, Lu, Meng, Yingying, An, Yalong, Yang, Gongshe, Li, Xiao. 2024. Single-cell RNA-seq reveals novel interaction between muscle satellite cells and fibro-adipogenic progenitors mediated with FGF7 signalling. In Journal of cachexia, sarcopenia and muscle, 15, 1388-1403. doi:10.1002/jcsm.13484. https://pubmed.ncbi.nlm.nih.gov/38751367/

2. Zinkle, Allen, Mohammadi, Moosa. 2019. Structural Biology of the FGF7 Subfamily. In Frontiers in genetics, 10, 102. doi:10.3389/fgene.2019.00102. https://pubmed.ncbi.nlm.nih.gov/30809251/

3. Meng, Hao, Liao, Zhiying, Ji, Yanting, Xu, Tao, Liu, Huisheng. 2024. FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection. In Signal transduction and targeted therapy, 9, 104. doi:10.1038/s41392-024-01790-8. https://pubmed.ncbi.nlm.nih.gov/38654010/

4. Milton, Christopher I, Selfe, Joanna, Aladowicz, Ewa, Kirkin, Vladimir, Shipley, Janet M. 2021. FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas. In Molecular oncology, 16, 1272-1289. doi:10.1002/1878-0261.13145. https://pubmed.ncbi.nlm.nih.gov/34850536/

5. Feng, Songwei, Ding, Bo, Dai, Zhu, Xiao, Zhongdang, Shen, Yang. 2024. Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter. In Journal of translational medicine, 22, 280. doi:10.1186/s12967-024-05085-y. https://pubmed.ncbi.nlm.nih.gov/38491511/