Piezo1-KO Mouse

Piezo1, a mechanosensitive ion channel, is essential for cardiovascular, lung, urinary, and immune functions [1]. It is widely distributed in human tissues and transduces mechanical stimuli into cellular signals, with its activation leading to various downstream effects, including calcium influx, which impacts numerous biological processes. Genetic models, such as KO/CKO mouse models, are valuable for studying Piezo1's functions.

In liver fibrosis, macrophages lacking Piezo1 show sustained inflammation and impaired efferocytosis, indicating Piezo1's role in promoting fibrosis resolution [2]. In Alzheimer's disease, microglia lacking Piezo1 exacerbate Aβ pathology and cognitive decline, while its pharmacological activation ameliorates these conditions, suggesting Piezo1 as a potential therapeutic target [3]. In kidney fibrosis, inhibition of Piezo1 in mouse models with unilateral ureter obstruction or folic acid treatment markedly ameliorates fibrosis, showing Piezo1's involvement in renal fibrosis progression [4]. In the brain, astrocytic Piezo1 deletion reduces hippocampal volume, impairs adult neurogenesis and cognitive functions, while overexpression enhances these processes [5]. In lymphatic growth, lymphatic-specific conditional Piezo1 knockout phenocopies sprouting defects in Orai1-or Klf2-knockout lymphatics, and postnatal deletion induces lymphatic regression [6]. In ventricular remodeling after myocardial infarction, knockdown or deletion of Piezo1 in thoracic dorsal root ganglion neurons lessens the severity of remodeling [7]. In hepatocellular carcinoma, Piezo1 knockdown suppresses tumor growth, angiogenesis, and lung metastasis in rat models [8].

In conclusion, Piezo1 is crucial for multiple biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has revealed its role in fibrosis, neurodegenerative diseases, kidney diseases, neurogenesis, lymphatic growth, ventricular remodeling, and cancer, providing insights for potential therapeutic strategies.

References:

1. Lai, Austin, Cox, Charles D, Chandra Sekar, Nadia, Peter, Karlheinz, Baratchi, Sara. 2021. Mechanosensing by Piezo1 and its implications for physiology and various pathologies. In Biological reviews of the Cambridge Philosophical Society, 97, 604-614. doi:10.1111/brv.12814. https://pubmed.ncbi.nlm.nih.gov/34781417/

2. Wang, Yang, Wang, Jin, Zhang, Jiahao, Miao, Naijun, Wang, Jing. 2024. Stiffness sensing via Piezo1 enhances macrophage efferocytosis and promotes the resolution of liver fibrosis. In Science advances, 10, eadj3289. doi:10.1126/sciadv.adj3289. https://pubmed.ncbi.nlm.nih.gov/38838160/

3. Hu, Jin, Chen, Qiang, Zhu, Hongrui, Zhang, Liang, Mo, Wei. 2022. Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer's disease. In Neuron, 111, 15-29.e8. doi:10.1016/j.neuron.2022.10.021. https://pubmed.ncbi.nlm.nih.gov/36368316/

4. Zhao, Xiaoduo, Kong, Yonglun, Liang, Baien, Li, Chunling, Wang, Weidong. 2022. Mechanosensitive Piezo1 channels mediate renal fibrosis. In JCI insight, 7, . doi:10.1172/jci.insight.152330. https://pubmed.ncbi.nlm.nih.gov/35230979/

5. Chi, Shaopeng, Cui, Yaxiong, Wang, Haiping, Zhong, Yi, Xiao, Bailong. 2022. Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions. In Neuron, 110, 2984-2999.e8. doi:10.1016/j.neuron.2022.07.010. https://pubmed.ncbi.nlm.nih.gov/35963237/

6. Choi, Dongwon, Park, Eunkyung, Yu, Roy P, Wong, Alex K, Hong, Young-Kwon. 2022. Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion. In Circulation research, 131, e2-e21. doi:10.1161/CIRCRESAHA.121.320565. https://pubmed.ncbi.nlm.nih.gov/35701867/

7. Sun, Meiyan, Mao, Sui, Wu, Chao, Hu, Ji, Zhang, Ye. 2024. Piezo1-Mediated Neurogenic Inflammatory Cascade Exacerbates Ventricular Remodeling After Myocardial Infarction. In Circulation, 149, 1516-1533. doi:10.1161/CIRCULATIONAHA.123.065390. https://pubmed.ncbi.nlm.nih.gov/38235590/

8. Li, Miao, Zhang, Xi, Wang, Mimi, Cui, Jiefeng, Ren, Zhenggang. 2022. Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma. In Cancer communications (London, England), 42, 1162-1184. doi:10.1002/cac2.12364. https://pubmed.ncbi.nlm.nih.gov/36181398/