Cell and Bioscience
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2022
·Vol. 12
·期 1
·1-13
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IF 9.584
Liu Qiang,Lei Xiaohua,Cao Zhenyu,Zhang Ju,Yan Likun,Fu Jie,Tong Qing,Qin Wei,Shao Yaoli,Liu Chun,Liu Zhiqiang,Wang Zicheng,Chu Yuan,Xu Ge,Liu Siyuan,Wen Xueyi,Yamamoto Hirofumi,Mori Masaki,Liang Xin. M.,Xu Xundi
Background Liver fibrosis represent a major global health care burden. Data emerging from recent advances suggest TRPM8, a member of the transient receptor potential (TRP) family of ion channels, plays an essential role in various chronic inflammatory diseases. However, its role in liver fibrosis remains unknown. Herein, we assessed the potential effect of TRPM8 in liver fibrosis. Methods The effect of TRPM8 was evaluated using specimens obtained from classic murine models of liver fibrosis, namely wild-type (WT) and TRPM8 −/− (KO) fibrotic mice after carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL) treatment. The role of TRPM8 was systematically evaluated using specimens obtained from the aforementioned animal models after various in vivo and in vitro experiments. Results Clinicopathological analysis showed that TRPM8 expression was upregulated in tissue samples from cirrhosis patients and fibrotic mice. TRPM8 deficiency not only attenuated inflammation and fibrosis progression in mice but also helped to alleviate symptoms of cholangiopathies. Moreover, reduction in S100A9 and increase in HNF4α expressions were observed in liver of CCl 4 - and BDL- treated TRPM8 −/− mice. A strong regulatory linkage between S100A9 and HNF4α was also noticed in L02 cells that underwent siRNA-mediated S100A9 knockdown and S100A9 overexpressing plasmid transfection. Lastly, the alleviative effect of a selective TRPM8 antagonist was confirmed in vivo. Conclusions These findings suggest TRPM8 deficiency may exert protective effects against inflammation, cholangiopathies, and fibrosis through S100A9-HNF4α signaling. M8-B might be a promising therapeutic candidate for liver fibrosis. Graphical Abstract
研究领域:
肝病学
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分子生物学
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药理学
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PubMed
高影响因子
CELL CALCIUM
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2026
·
IF 4
Zi-Yang Huang,Yu-Yun Zhou,Xin-Ni Sun,Yi-Ran Ye,Fei-Fei Huang,Jie Sheng,Dan-Yang Zou,Ting-Ting Tang,Zi-Ying Yang,Tong-Zhen Weng,Xin-Rui Ling-Hu,Wai Hou Tang,Yun-Xin Zhu,Lei Chen,Su Qu,Wen-Liang Zhou,Yi-Lin Zhang
The epididymis establishes a unique hyper-potassium luminal microenvironment essential for sperm maturation and storage, which is largely orchestrated by epididymal epithelial ion transport. Although the transient receptor potential melastatin 8 (TRPM8) is broadly expressed across various organ systems, its physiological role in male reproduction has remained largely unexplored. This study demonstrated that TRPM8 was predominantly expressed in rat epididymal epithelial cells. Activation of TRPM8 by either the exogenous agonist WS-12 or the endogenous hormone testosterone triggered a decrease in short-circuit current ( I SC ) response in primary cultured rat epididymal epithelial cells. This I SC response was suppressed by removal of extracellular K + or by pharmacological inhibition of Ca 2+ -activated potassium channels (K Ca ), Na + -K + ATPase or the Na + -K + -Cl − cotransporter, indicating that TRPM8 mediated transepithelial K + secretion in a Ca 2+ -dependent manner. Consistently, TRPM8 activation increased intracellular Ca 2+ concentration in primary rat epididymal epithelial cells, which could be abolished by the removal of extracellular Ca 2+ . An in vivo study showed functional TRPM8 deficiency disrupted the luminal hyper-potassium microenvironment in rat epididymis. Moreover, impaired sperm motility and reduced male fertility were observed in TRPM8-deficient rats, which could be rescued by restoring luminal hyper-potassium microenvironment through K Ca activation. Overall, this study elucidates a crucial role for TRPM8 in establishing the epididymal hyper-potassium microenvironment, offering valuable insights into the physiological function of TRPM8 in male reproductive health and disease.
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高影响因子
Frontiers in Medicine
·
2024
·
IF 3.1
Zhongzhu Ai,Dongfeng Yuan,Jingyi Cai,Ruotong Dong,Wei Liu,Daonian Zhou
Background: Pruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.Methods: A chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.Results: The study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.Conclusion: MHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.
研究领域:
药理学
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神经科学
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皮肤病学
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分子生物学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2025
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IF 9.8
Yanyan Cao,Meng Tao,Anan Xu,Zheng Tu,Shanshan Wang,Qinyan Yu,Sixu Li,Zhengquan Liu
Black tea contains sweet aroma compounds (SACs) with sweetening potential. However, a systematic understanding of their composition, enhancing effects, and underlying mechanisms is lacking. This study identified 14 key SACs in global sweet-aroma black teas using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry. Electronic tongue and sensory validation confirmed their sweetness-enhancing effects in a sugar-free black tea beverage and revealed their inherent taste properties (sweetness, astringency, pungency, and cooling). Molecular docking and dynamics simulation elucidated the stable bindings of T1R2/T1R3-benzeneacetaldehyde/ β -damascenone, α -amylase-benzeneacetaldehyde, TRPV1-geraniol, and TRPM8-methyl salicylate, mediated by hydrogen bonding and hydrophobic interactions. These protein-ligand complexes were proposed to modulate sweetness, sweet aftertaste, heat-evoked sweetness, and cooling-enhanced sweetness, respectively. Consequently, this study demonstrates that SACs enhance sweetness through cross-modal interactions and inherent taste properties, providing novel mechanistic insights and actionable strategies for flavor optimization in tea beverages and other food products.
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高影响因子
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