Lats2, also known as large tumor suppressor kinase 2, is a core kinase of the Hippo pathway. The Hippo pathway is evolutionarily conserved and regulates numerous biological processes like cell growth, fate decision, organ size control, and regeneration [1]. Lats2 is crucial in this pathway, controlling transcriptional programs related to cell proliferation, survival, and more. Genetic models, such as KO/CKO mouse models, have been valuable in studying its functions.

In endothelial cell-specific Lats2 knockout mice, it was found that Lats2 inactivation induces myofibroblast formation, leading to extensive fibrosis and osteosclerosis in the bone marrow, impairing its function [2]. In proximal tubular Lats2 conditional knockout mice, Lats2 deficiency exacerbated ischemia/reperfusion injury-induced renal maladaptive repair through upregulating p53 [3]. Systemic Lats2+/- mice showed attenuated cardiac hypertrophy, dysfunction, interstitial fibrosis, and apoptosis in response to transverse aortic constriction, suggesting Lats2 promotes heart failure via p53-dependent apoptosis during pressure overload [4].

In conclusion, Lats2, as a key component of the Hippo pathway, plays essential roles in multiple biological processes. The use of KO/CKO mouse models has revealed its significance in diseases such as bone marrow fibrosis, renal maladaptive repair, and heart failure, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Ma, Shenghong, Meng, Zhipeng, Chen, Rui, Guan, Kun-Liang. 2019. The Hippo Pathway: Biology and Pathophysiology. In Annual review of biochemistry, 88, 577-604. doi:10.1146/annurev-biochem-013118-111829. https://pubmed.ncbi.nlm.nih.gov/30566373/

2. Sivaraj, Kishor K, Majev, Paul-Georg, Dharmalingam, Backialakshmi, Schneider, Rebekka K, Adams, Ralf H. 2024. Endothelial LATS2 is a suppressor of bone marrow fibrosis. In Nature cardiovascular research, 3, 951-969. doi:10.1038/s44161-024-00508-x. https://pubmed.ncbi.nlm.nih.gov/39155965/

3. Zhang, Chi, Zheng, Zhihuang, Xu, Kexin, Wu, Huijuan, Liu, Jun. 2023. Proximal Tubular Lats2 Ablation Exacerbates Ischemia/Reperfusion Injury (IRI)-Induced Renal Maladaptive Repair through the Upregulation of P53. In International journal of molecular sciences, 24, . doi:10.3390/ijms242015258. https://pubmed.ncbi.nlm.nih.gov/37894939/

4. Shao, Dan, Zhai, Peiyong, Hu, Chengchen, Del Re, Dominic, Sadoshima, Junichi. 2021. Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload. In Scientific reports, 11, 23469. doi:10.1038/s41598-021-02846-3. https://pubmed.ncbi.nlm.nih.gov/34873220/