Wnt7a, a member of the Wnt family, plays crucial roles in multiple biological processes. It is involved in the Wnt/β -catenin signaling pathway, which is vital for organ development, cell proliferation, and differentiation. Wnt7a is important for angiogenesis, maintaining tissue integrity, and muscle function, making it biologically significant [1-4]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In pulmonary arterial hypertension (PAH), global Wnt7a +/- mice in hypoxia showed higher pulmonary pressures and severe right-ventricular and lung vascular remodelling. PAH patient-derived pulmonary microvascular endothelial cells (PMVECs) had reduced Wnt7a expression, and Wnt7a -/- PMVECs exhibited an insufficient angiogenic response to VEGF-A, suggesting Wnt7a deficiency contributes to PAH-related small vessel loss [1]. In skeletal muscle, Wnt7a-deleted WT and mdx mice had marked deficiencies in muscle regeneration following injury, indicating its requirement for muscle repair [2]. In idiopathic pulmonary fibrosis (IPF), neutralizing antibodies against Wnt7A or a Frizzled signaling inhibitor abolished basal cell-induced fibroblast activation and attenuated lung fibrosis in mice, highlighting Wnt7a's role in fibrogenesis [3].

In conclusion, Wnt7a is essential for angiogenesis, muscle regeneration, and in the context of diseases like PAH and IPF, its deficiency or inappropriate regulation contributes to disease progression. The use of Wnt7a KO/CKO mouse models has significantly enhanced our understanding of its role in these biological processes and disease conditions [1,2,3].

References:

1. Chakraborty, Ananya, Nathan, Abinaya, Orcholski, Mark, Cornfield, David N, de Jesus Perez, Vinicio A. 2023. Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension. In The European respiratory journal, 61, . doi:10.1183/13993003.01625-2022. https://pubmed.ncbi.nlm.nih.gov/37024132/

2. Gurriaran-Rodriguez, Uxia, Kodippili, Kasun, Datzkiw, David, Rejas, Maria Teresa, Rudnicki, Michael A. 2024. Wnt7a is Required for Regeneration of Dystrophic Skeletal Muscle. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.01.24.577041. https://pubmed.ncbi.nlm.nih.gov/38328077/

3. Huang, Guanling, Liang, Jiurong, Huang, Kevin, Noble, Paul W, Jiang, Dianhua. . Basal Cell-derived WNT7A Promotes Fibrogenesis at the Fibrotic Niche in Idiopathic Pulmonary Fibrosis. In American journal of respiratory cell and molecular biology, 68, 302-313. doi:10.1165/rcmb.2022-0074OC. https://pubmed.ncbi.nlm.nih.gov/36318668/