Smooth muscle research is at the forefront of translational science, bridging the gap between basic molecular discoveries and clinical applications. The symposium “Muscle and Pathology/Health: Frontiers of Translational Research” at the 66th Annual Meeting of Japan Society of Smooth Muscle Research showcased recent advances in this field. The presentations highlighted diverse topics, including molecular targeting in malignant hyperthermia, the therapeutic potential of probiotics in inflammatory bowel disease, sex differences in pulmonary hypertension and the impact of dietary components on vascular health. These studies underscore the importance of precision therapies, personalized medicine and functional foods in understanding and managing diseases. As technological innovations continue to drive research, the symposium provided insight into future directions, such as developing targeted molecular therapies, leveraging probiotics for systemic effects, expanding sex-based studies, and industrializing outcomes of basic science. The findings presented offer promising avenues for new treatment strategies that could revolutionize smooth muscle-related healthcare, emphasizing the potential for improved patient outcomes through translational research.

Thermoregulation is essential for maintaining homeostasis in mammals under various environmental conditions. Impairment of this function can result in severe conditions, such as fever, heat stroke, and malignant hyperthermia (MH). In this review, we will focus on the role of the type 1 ryanodine receptor (RYR1), a Ca²⁺ release channel that is crucial for excitation-contraction coupling in skeletal muscles. Mutations in RYR1 are associated with muscle disorders, including MH, which is characterized by dysregulated Ca²⁺-induced Ca²⁺ release (CICR). Recent advances from genetically engineered mouse models of MH have provided new insights into the pathophysiological mechanisms underlying anesthetic- and heat-induced episodes, and revealed a heat-induced Ca²⁺ release (HICR) mechanism mediated by RYR1. Experimental evidences demonstrate that anesthetics induce simultaneous increases in cellular temperature and cytosolic Ca²⁺ concentration. Therefore, this review proposes that an increase in cellular temperature triggers further Ca²⁺ release via HICR, establishing a positive feedback loop that sustains excessive heat production during MH crises.

Inflammatory bowel disease (IBD) is a term that describes disorders involving long-standing inflammation of tissues in the digestive tract. The onset and exacerbation of IBD is linked to multiple factors, including genetic and immunological influences, diet, and gut bacteria. Additionally, it is associated with a high risk of cancer. Research shows that the longer a person is breastfed, the lower their risk of developing IBD, highlighting the impact of human breast milk components on intestinal bacteria. Human breast milk contains many bioactive components, such as lactoferrin and milk oligosaccharides, are known to be effective in preventing and treating IBD. Probiotics are defined as live microorganisms that provide beneficial effects on the host by altering the balance of indigenous intestinal bacteria. While probiotics, such as lactic acid bacteria and bifidobacteria, have been clinically applied in IBD treatment, there are currently no reports on the application of human breast milk-derived probiotics for this purpose. We clarified the preventive and therapeutic effects of human breast milk-derived probiotics on IBD, as well as the underlying mechanisms. This review highlights the importance of breastfeeding to prevent IBD, and focuses on the therapeutic effects of human breast milk-derived probiotics in IBD. These bioactive compounds in human breast milk are instrumental in establishing a beneficial gut microbiota and promoting proper immune system maturation during early life.

Pulmonary arterial hypertension (PAH) is a rare and fatal cardiovascular disease characterized by pulmonary vascular remodeling, leading to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure (PAP). Elevated PAP induces right ventricular hypertrophy and eventually progresses to right heart failure. Pulmonary vascular remodeling is primarily caused by the excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) in the medial layer. This is mediated by the binding of growth factors to their specific receptor tyrosine kinases. To date, several growth factors, including epidermal growth factor, fibroblast growth factor, insulin-like growth factor, platelet-derived growth factor (PDGF), transforming growth factor-β, and vascular endothelial growth factor, have been implicated in the development of PAH. Our previous studies have demonstrated that the upregulated expression of Ca²⁺-sensing receptors in PASMCs contributes to the development of PAH. This upregulation was induced by increased PDGF levels in PASMCs from PAH patients. Therefore, imatinib (a tyrosine kinase inhibitor including PDGF receptors) and corosolic acid (with inhibitory effects of PDGF signaling) suppressed the excessive proliferation and migration of PASMCs from PAH patients. These treatments also ameliorated pulmonary vascular remodeling in pulmonary hypertensive rats. This review focuses on the pathological roles of growth factors, especially PDGF, in the pathogenesis and progression of PAH.

In Japan, there is an approximate 10 year gap between average life expectancy and healthy life expectancy, which represents a decade characterized by poor health. To shorten this period and promote healthy aging, we searched for food ingredients that promote vascular health. Focusing on nitric oxide (NO) released by vascular endothelial cells, we first established an evaluation method to measure the NO production capacity of the vascular endothelium in real-time. This helped identify Sakurajima-radish (Raphanus sativus cv. Sakurajima Daikon), which promotes NO production in vascular endothelial cells. The ability of Sakurajima-radish to induce NO production was observed in both the edible part of the enlarged root and the leaves to an equal extent. We identified the active component, trigonelline, and found that Sakurajima-radish contains much higher amounts of trigonelline than other natural products. There was no statistically significant difference in trigonelline content among the varieties of Sakurajima-radish distributed across Kagoshima Prefecture, nor was there any significant difference among the production areas within Kagoshima Prefecture, including outlying islands. The trigonelline content of Sakurajima-radish remained relatively stable across most cooking methods. A clinical study involving healthy individuals showed that Sakurajima-radish consumption (170 g/day for 10 days) caused a significant increase in flow-mediated dilation and blood trigonelline levels. This article elucidates the potential of Sakurajima-radish as a functional food that can be stored, cooked, and eaten in various forms with significant health benefits contributing to improved vascular function.