机械敏感性离子通道PIEZO1调控NLRP3信号通路影响克罗恩病肠道炎症的机制探究
关键词：克罗恩病；PIEZO1；NLRP3信号通路；肠道炎症；机制探究
Abstract: Crohn's disease is a chronic digestive tract disease that is influenced by multiple environmental and genetic factors, with the immune and inflammatory responses playing critical roles in its onset and development. The mechanically-sensitive ion channel PIEZO1 is expressed in multiple cell types and participates in various physiological and pathological processes. In this study, we investigated the role of PIEZO1 in Escherichia coli-induced Crohn's disease intestinal inflammation and the molecular mechanisms by which it regulates the NLRP3 signaling pathway. Results showed that PIEZO1 was highly expressed in human intestinal samples and was correlated with the severity of Crohn's disease. PIEZO1-deficient mice exposed to E. coli exhibited decreased NLRP3 expression and inflammatory cytokine secretion in intestinal epithelial cells, as well as significantly reduced intestinal inflammation. Additionally, PIEZO1 activation increased intracellular calcium concentrations, subsequently promoting NLRP3 signal pathway activation. On the other hand, PIEZO1 deficiency or inhibiti
on inhibited signal pathway activation of NLRP3. In summary, these results indicated that PIEZO1 is an important regulator of intestinal inflammation in Crohn's disease, which affects inflammation through regulating the activation of the NLRP3 signaling pathway. These findings provide new insights and a foundation for further mechanism studies and the design of novel therapeutic strategies in this field.
Keywords: Crohn's disease; PIEZO1; NLRP3 signaling pathway; intestinal inflammation; mechanism stud。
reactive materials studiesCrohn's disease (CD) is a chronic inflammatory disorder that affects the intestinal tract, leading to significant morbidity and mortality. The pathogenesis of CD is multifactorial, involving genetic, environmental, and immunological factors. However, the molecular mechanisms underlying CD pathogenesis are not fully understood.
Recently, PIEZO1 has emerged as a key player in the regulation of inflammation, mechanotransduction, and cellular signaling. In the context of CD, PIEZO1 has been shown to be upregulated in patients' intestinal tissues, where it promotes the production of
pro-inflammatory cytokines and chemokines.
More importantly, PIEZO1 has been demonstrated to regulate the activation of the NLRP3 inflammasome, a large intracellular complex that mediates the production of pro-inflammatory cytokines, such as IL-1β and IL-18. In CD, the dysregulated activation of the NLRP3 inflammasome is a critical driver of intestinal inflammation.
By modulating the activation of the NLRP3 pathway, PIEZO1 can promote or suppress inflammation, depending on the context. Specifically, PIEZO1 activation induces the production of reactive oxygen species (ROS), which are required for NLRP3 activation. Conversely, inhibition or knockdown of PIEZO1 attenuates NLRP3 activation, leading to reduced inflammation.
Collectively, these findings suggest that PIEZO1 plays a crucial role in the pathogenesis of CD by regulating intestinal inflammation, likely through the modulation of NLRP3 activation. As such, targeting PIEZO1 and its downstream signaling pathways may represent a promising therapeutic strategy for CD and other chronic inflammatory diseases。
In addition to its role in CD, PIEZO1 has also been implicated in several other disease processes. For example, recent studies have suggested that PIEZO1 may play a role in the development of osteoarthritis (OA). OA is a chronic degenerative joint disease characterized by the breakdown of articular cartilage and subchondral bone, leading to pain, stiffness, and loss of mobility.
One study found that mechanical stress induced by compressive loading of joint cartilage led to increased PIEZO1 expression and activation, which in turn activated downstream pathways involved in the production of inflammatory cytokines and extracellular matrix-degrading enzymes. The authors concluded that PIEZO1 may be a key mediator of mechanical stress-induced cartilage degeneration in OA.
Similarly, PIEZO1 has also been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), a progressive and often fatal disease characterized by vascular remodeling and increased vascular resistance in the pulmonary circulation. In a mouse model of PAH, inhibition of PIEZO1 with a small molecule inhibitor led to reduced pulmonar
y vascular remodeling and improved hemodynamic parameters, suggesting that PIEZO1 may be a potential therapeutic target for this condition.
Overall, these findings highlight the broad importance of PIEZO1 in a variety of disease processes, and suggest that targeting this ion channel may have therapeutic potential in a range of chronic inflammatory and degenerative conditions. However, further research is needed to fully elucidate the mechanisms by which PIEZO1 contributes to these diseases, and to develop safe and effective therapeutic strategies that target this channel。
In addition to the diseases discussed above, recent studies have also suggested a potential role for PIEZO1 in cancer. PIEZO1 expression has been shown to be upregulated in various types of cancer cells, including breast, lung, and prostate cancer cells (13, 14). Moreover, activation of PIEZO1 has been shown to promote cancer cell migration and invasion, while inhibition of PIEZO1 has been shown to suppress these processes (13, 14). These findings suggest that targeting PIEZO1 may be a promising approach for inhibiting cancer metastasis.

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