Fbln2-KO Mouse

Fbln2, or fibulin-2, is a secreted extracellular matrix (ECM) glycoprotein. It is essential for basement membrane (BM) integrity in mammary epithelium [2]. It has been implicated in multiple biological processes and disease-related pathways, such as chondrogenic differentiation, apoptosis and proliferation of cranial neural crest cells (CNCCs) through the bone morphogenic protein (BMP) signaling pathway [1].

A fbln2 knockout zebrafish line was established to study its role in craniofacial cartilage development. The knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies, showing that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of CNCCs, and downregulated the BMP signaling pathway [1]. In the context of idiopathic pulmonary fibrosis (IPF), knockdown of FBLN2 in human lung fibroblast-derived MRC-5 cells inhibited TGF-β1-induced proliferation, migration and fibrosis by downregulating vitronectin (VTN) via focal adhesion kinase (FAK) signaling [3]. In gastric cancer, overexpression of FBLN2 reduced cell proliferation and metastasis, while knockdown enhanced these processes, and it was shown to act through the TGFβ/TGIF2 axis [4].

In conclusion, Fbln2 plays crucial roles in multiple biological processes. Studies using gene-knockout models, such as the fbln2 knockout zebrafish, have revealed its importance in craniofacial development, as well as its potential roles in diseases like Goldenhar syndrome, IPF, and gastric cancer. These models have provided valuable insights into the underlying molecular mechanisms, offering potential targets for disease treatment and prevention.

References:

1. Niu, Xiaomin, Zhang, Fuyu, Gu, Wei, Zhang, Bo, Chen, Xiaowei. 2024. FBLN2 is associated with Goldenhar syndrome and is essential for cranial neural crest cell development. In Annals of the New York Academy of Sciences, 1537, 113-128. doi:10.1111/nyas.15183. https://pubmed.ncbi.nlm.nih.gov/38970771/

2. WalyEldeen, Amr Ahmed, Sabet, Salwa, Anis, Shady E, Stein, Torsten, Ibrahim, Ayman M. 2024. FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer. In Breast cancer research and treatment, 208, 673-686. doi:10.1007/s10549-024-07447-y. https://pubmed.ncbi.nlm.nih.gov/39110274/

3. Zhang, Yanju, Zhang, Weishuai, Zhang, Rui, Xia, Yunfei. 2022. Knockdown of FBLN2 suppresses TGF-β1-induced MRC-5 cell migration and fibrosis by downregulating VTN. In Tissue & cell, 81, 102005. doi:10.1016/j.tice.2022.102005. https://pubmed.ncbi.nlm.nih.gov/36608640/

4. Zhou, Ming, Mao, Xiaozhe, Shen, Kanger, Huang, Ziyi, Li, Rui. 2025. FBLN2 inhibits gastric cancer proliferation and metastasis via the TGFβ/TGIF2 pathway. In Pathology, research and practice, 269, 155899. doi:10.1016/j.prp.2025.155899. https://pubmed.ncbi.nlm.nih.gov/40168772/