Article
Biochemistry & Molecular Biology
Junping Fan, Linghan Hu, Zongwei Yue, Daohong Liao, Fusheng Guo, Han Ke, Daohua Jiang, Yong Yang, Xiaoguang Lei
Summary: The TRPV3 channel has important roles in skin physiology. Trpvicin, identified in this study, is a potent and subtype-selective inhibitor of TRPV3, which shows pharmacological potential in the inhibition of itch and hair loss. The research provides mechanistic insights into the inhibition of TRPV3 by Trpvicin and supports drug development targeting TRPV3.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biology
Yu Yamanoi, Jing Lei, Yasunori Takayama, Shigekuni Hosogi, Yoshinori Marunaka, Makoto Tominaga
Summary: The chloride channel anoctamin1 is activated by calcium influx through transient receptor potential vanilloid 3 (TRPV3), leading to chloride influx and enhancement of wound healing in keratinocytes.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Arthur Neuberger, Kirill D. Nadezhdin, Alexander I. Sobolevsky
Summary: This study reveals the structural basis of TRPV3 binding with the local anesthetic, dyclonine, and proposes a mechanism for TRPV3 inhibition. This finding is of great significance for the design of new TRPV3-targeting drugs.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Yaotao Guo, Yajuan Song, Wei Liu, Tong Wang, Xianjie Ma, Zhou Yu
Summary: TRPV3, a non-selective cation channel, is highly expressed in keratinocytes in the skin. It plays a role in multiple physiological and pathological processes of the skin, including itching, heat pain, and hair development. Recent studies suggest that cytokines and EGFR signaling pathways may be involved in TRPV3 functions. However, conflicting results have been reported regarding the role of TRPV3 in heat pain. Additionally, TRPV3 has been found to promote skin regeneration, indicating its potential as a target for regulating skin regeneration.
Article
Biology
Qiang Liu, Jin Wang, Xin Wei, Juan Hu, Conghui Ping, Yue Gao, Chang Xie, Peiyu Wang, Peng Cao, Zhengyu Cao, Ye Yu, Dongdong Li, Jing Yao
Summary: The study found that the clinical medication dyclonine can inhibit the TRPV3 channel, rescuing cell death caused by gain-of-function mutations and suppressing itch symptoms in a mouse model. By molecular simulations and mutagenesis, key residues in the TRPV3 pore region were identified that could affect the inhibitory efficiency of dyclonine.
Article
Biochemistry & Molecular Biology
Arthur Neuberger, Kirill D. Nadezhdin, Eleonora Zakharian, Alexander Sobolevsky
Summary: TRPV3, predominantly expressed in skin keratinocytes, can be competitively inhibited by osthole through converting the channel pore into a previously unidentified conformation with widely open selectivity filter and closed intracellular gate. The cryo-EM structures of TRPV3 in complex with osthole provide insight into the competitive inhibition mechanism and can serve as a template for drug design targeting TRPV3-associated diseases.
Article
Multidisciplinary Sciences
Lan Zhang, Hongliang Zeng, Ling Jiang, Chuhan Fu, Yushan Zhang, Yibo Hu, Xiaolin Zhang, Lu Zhu, Fan Zhang, Jinhua Huang, Jing Chen, Qinghai Zeng
Summary: Global warming and rising temperature lead to increased heat stress, which affects inflammation, aging, and skin melanogenesis. Heat stress promotes melanogenesis in pigment cells by increasing the paracrine effects of keratinocytes, which is mediated by the activation of the Hedgehog (Hh) signaling pathway. TRPV3 agonists activate the Hh signaling in keratinocytes and enhance its paracrine effect on melanogenesis. The heat-induced activation of the Hh signaling is dependent on TRPV3-mediated Ca2+ influx. These findings provide insights into the mechanisms of heat-induced skin pigmentation.
Review
Cell Biology
Hanxiao Yin, Mingzheng Hu, Dengwen Li
Summary: The epidermis is a barrier in the outermost layer of the skin that protects against pathogens. Basal keratinocytes, acting as stem cells, are crucial for epidermal development and skin damage recovery. Understanding the molecular mechanism of basal keratinocytes in epidermal development and stratification is important for preventing and treating skin lesions.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thi Huyen Dang, Ji Yeong Kim, Hyun Jong Kim, Byung Joo Kim, Woo Kyung Kim, Joo Hyun Nam
Summary: This study found that alpha-mangostin effectively inhibits TRPV3, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results suggest that alphamangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dermatology
Zhongya Song, Xi Chen, Qian Zhao, Vesna Stanic, Zhimiao Lin, Shuxia Yang, Ting Chen, Jiang Chen, Yong Yang
Summary: The gain-of-function mutations in the TRPV3 gene can lead to hair loss in patients with Olmsted syndrome. The mechanism involves premature differentiation of follicular keratinocytes, resulting in decreased hair follicle stem cells and impaired regeneration of hair follicles. The study highlights the importance of postmitotic follicular keratinocytes in driving hair loss in patients with Olmsted syndrome.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tao Zhong, Xiaofan Wu, Wei Xie, Xiangrui Luo, Ting Song, Shuang Sun, Youguang Luo, Dengwen Li, Min Liu, Songbo Xie, Jun Zhou
Summary: ENKD1 is identified as a critical regulator of epidermal stratification by modulating the cell-division orientation of basal keratinocytes and promoting astral microtubule stability. Depletion of ENKD1 leads to thinner epidermis and defective spindle orientation, which can be rescued by introducing the microtubule-binding domain of ENKD1.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Cell Biology
Kunwei Wu, David Castellano, Qingjun Tian, Wei Lu
Summary: The study reveals distinct roles of GluN2A and GluN2B-NMDA receptors in regulating tonic inhibition in hippocampal neurons, with NMDAR subunit-specific mechanisms at play. Tonic inhibition is modulated by various factors in both physiological and pathological conditions.
Article
Biology
Keigo Fujita, Yutaka Shindo, Yuji Katsuta, Makiko Goto, Kohji Hotta, Kotaro Oka
Summary: This study demonstrates that Mg2+ protects skin cells from oxidative stress caused by ROS, which are generated after exposure to ultraviolet irradiation. The increase in cytosolic Mg2+ levels in response to H2O2 indicates that Mg2+ plays a role in combating oxidative stress. In addition, Mg2+ supplementation attenuated H2O2-induced cell death.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Kunwei Wu, Wenyan Han, Qingjun Tian, Yan Li, Wei Lu
Summary: Shisa7 plays a critical role in regulating tonic inhibition in hippocampal neurons by influencing alpha 5-GABA(A)R exocytosis, which requires the involvement of PKA and is essential for activity-dependent regulation and oscillations during the sleep/wake cycle.
Article
Biochemistry & Molecular Biology
Si-Qi Chen, Xue-Yan Chen, Ying-Zhe Cui, Bing-Xi Yan, Yuan Zhou, Zhao-Yuan Wang, Fan Xu, Yan-Zhou Huang, Yu-Xin Zheng, Xiao-Yong Man
Summary: Recent studies have shown that there are dense sensory nerve fibers in psoriatic lesions, which are closely connected to immune cells and keratinocytes. These nerve fibers play a vital role in the progression of psoriasis. Neurological intervention may be a new treatment strategy for psoriasis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Immunology
Nicole R. Wong, Jay Mohan, Benjamin J. Kopecky, Shuchi Guo, Lixia Du, Jamison Leid, Guoshuai Feng, Inessa Lokshina, Oleksandr Dmytrenko, Hannah Luehmann, Geetika Bajpai, Laura Ewald, Lauren Bell, Nikhil Patel, Andrea Bredemeyer, Carla J. Weinheimer, Jessica M. Nigro, Attila Kovacs, Sachio Morimoto, Peter O. Bayguinov, Max R. Fisher, W. Tom Stump, Michael Greenberg, James A. J. Fitzpatrick, Slava Epelman, Daniel Kreisel, Rajan Sah, Yongjian Liu, Hongzhen Hu, Kory J. Lavine
Summary: Recent studies have revealed that CCR2(-) tissue-resident macrophages play a crucial role in chronic heart failure, essential for maintaining cardiac function. These macrophages interact with cardiomyocytes and are activated through a transient receptor potential vanilloid 4 (TRPV4)-dependent pathway, controlling the expression of growth factors.
Article
Allergy
Anna M. Trier, Madison R. Mack, Avery Fredman, Masato Tamari, Aaron M. Ver Heul, Yonghui Zhao, Changxiong J. Guo, Oshri Avraham, Zachary K. Ford, Landon K. Oetjen, Jing Feng, Carina Dehner, Dean Coble, Asima Badic, Satoru Joshita, Masato Kubo, Robert W. Gereau, Jennifer Alexander-Brett, Valeria Cavalli, Steve Davidson, Hongzhen Hu, Qin Liu, Brian S. Kim
Summary: IL-33 signaling may play a critical role in the development of chronic itch, depending on the tissue microenvironment.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Anesthesiology
Erik G. Larsen, Tiffany S. Cho, Matthew L. McBride, Jing Feng, Bhagyashree Manivannan, Cynthia Madura, Nathaniel E. Klein, Elizabeth B. Wright, Edward S. Wickstead, Hector D. Garcia-Verdugo, Chelsea Jarvis, Rajesh Khanna, Hongzhen Hu, Tally M. Largent-Milnes, Martha R. C. Bhattacharya
Summary: This study reveals the crucial role of TMEM184B protein in the specification of itch-sensitive neurons. TMEM184B promotes adult somatosensation through developmental Wnt signaling and the expression of proper pruriceptive genes.
Article
Neurosciences
Jing Feng, Tim J. Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J. Spencer, Hongzhen Hu
Summary: Through chemogenetic strategy, reduction of CAL neurons in the colon led to decreased colonic length and pellet sizes without overt inflammation. Interestingly, there was an increase in frequency and decrease in size of colonic motor complexes (CMCs) with lack of preferential anterograde migration. This suggests that calretinin neurons may play a role in pacing, force, and polarity of CMCs in the large bowel.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Zili Xie, Jing Feng, Tao Cal, Ronald McCarthy, Mark D. Eschbach, Yuhui Wang, Yonghui Zhao, Zhihua Yi, Kaikai Zang, Yi Yuan, Xueming Hu, Fengxian Li, Qin Liu, Aditi Das, Sarah K. England, Hongzhen Hu
Summary: Pain originating from the female reproductive tract is difficult to treat, and the molecular and cellular mechanisms underlying it are not fully understood. This study discovered that 2-and 4-hydroxylated estrogen metabolites can increase nociceptor hyperactivity through TRPA1 and TRPV1 channels, leading to enhanced pain perception. The findings highlight the critical role of TRPA1 in estrogen-induced uterine pain-like behaviors.
Article
Radiology, Nuclear Medicine & Medical Imaging
Yanbo Yu, Hao Jiang, Qianwa Liang, Lin Qiu, Tianyu Huang, Hongzhen Hu, Vadim Y. Bolshakov, Joel S. Perlmutter, Zhude Tu
Summary: In this study, a new C-11 radiotracer [C-11]HC070 was synthesized and evaluated for imaging TRPC5 in rodents and nonhuman primates. The results showed that [C-11]HC070 has high brain uptake and good brain washout pharmacokinetics.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Cell Biology
Jing Feng, Yonghui Zhao, Zili Xie, Kaikai Zang, Sanja Sviben, Xueming Hu, James A. J. Fitzpatrick, Lu Wen, Yifei Liu, Ting Wang, Katy Lawson, Qin Liu, Yan Yan, Xinzhong Dong, Liang Han, Gregory F. Wu, Brian S. Kim, Hongzhen Hu
Summary: This study reveals the mechanism behind the itch-scratch cycle in chronic itch. Mechanical stimulation of the skin activates Piezo2 channels on Merkel cells, leading to spontaneous itch in dry skin. The study also demonstrates structural alterations between pruriceptor nerve endings and Merkel cells in dry skin. These findings provide insights into the pathophysiology of chronic itch and may contribute to the development of new treatments.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Wen Zhang, Mengze Lyu, Nicholas J. Bessman, Zili Xie, Mohammad Arifuzzaman, Hiroshi Yano, Christopher N. Parkhurst, Coco Chu, Lei Zhou, Gregory G. Putzel, Ting-Ting Li, Wen-Bing Jin, Jordan Zhou, Hongzhen Hu, Amy M. Tsou, Chun-Jun Guo, David Artis
Summary: Research has found that nociceptive neurons have a significant impact on intestinal inflammation. Disrupted nociception leads to more severe inflammation and defective tissue repair processes. This disruption also causes changes in the intestinal microbiota and dysbiosis, while certain bacteria can promote tissue protection. Additionally, abnormal nociceptor gene expression was observed in intestinal biopsies from patients with inflammatory bowel diseases.
Article
Neurosciences
Timothy J. Hibberd, Wai Ping Yew, Kelsi N. Dodds, Zili Xie, Lee Travis, Simon J. Brookes, Marcello Costa, Hongzhen Hu, Nick J. Spencer
Summary: This study comprehensively quantified CGRP+ myenteric neurons in mouse colon, which aligns with the expected range of an intrinsic primary afferent neuron (IPAN) marker.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Review
Physiology
Jing Feng, Zili Xie, Hongzhen Hu
Summary: This Review discusses the expression and function of ion channels in immune cells, non-immune cells, and neuroimmune interactions in the gut. It also explores the role of ion channels in maintaining intestinal immune homeostasis and contributing to the development of autoimmune disorders. Understanding ion channel signaling in immune-related pathways will aid in the development of therapeutic approaches for intestinal inflammation.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Neurosciences
Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu
Summary: By ablating the sensory channels TRPV1 and Piezo2 from colon-innervating neurons, the visceromotor responses (VMR) induced by colorectal distention (CRD) are significantly reduced in mice. Selective ablation of Piezo2 channels in TRPV1 lineage neurons reduces mechanically evoked visceral afferent action potential firing and CRD-induced VMR under physiological conditions, as well as in mouse models of zymosan-induced IBS and partial colon obstruction (PCO). These findings demonstrate the important role of the mechanosensitive Piezo2 channels in TRPV1-lineage neurons in visceral mechanosensitivity and nociception under physiological conditions, as well as in visceral hypersensitivity under pathological conditions.
Article
Neurosciences
Nick J. Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu
Summary: In recent years, there has been increasing interest in understanding the communication between the gut and the brain. New data suggests that the sensory nerve pathways between the two may have a more significant impact on health and disease than previously assumed. While sensory nerve endings in the skin have been extensively studied, there is a lack of knowledge about most types of visceral afferents, especially those that innervate abdominal organs like the gut. Recent studies have identified nerve endings of spinal afferents in visceral organs, emphasizing their role in pain perception from the gut to the brain. Surprisingly, the majority of these spinal afferent nerve endings in the gut express the TRPV1 ion channel, commonly associated with nociceptive neurons. Furthermore, these nerve endings are activated at low thresholds within the normal physiological range, suggesting a complex nature of visceral nociception. This highlights the need to redefine nociceptors in the gut, which may involve multiple morphological types of spinal afferent nerve endings.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Ping Lu, Yonghui Zhao, Zili Xie, Huan Zhou, Xinzhong Dong, Gregory F. Wu, Brian S. Kim, Jing Feng, Hongzhen Hu
Summary: Although touch and itch are coded by different neuronal populations, light touch can provoke itch in the presence of pruritogens, resulting in a phenomenon called alloknesis. This study reveals the cellular and molecular mechanisms involved in pruritogen-induced mechanical itch sensitization, showing that histamine and chloroquine activate specific prurioceptors and sensitize Piezo2 channel function through the PLC and PKC8 signaling pathways. Understanding this signaling axis could provide insights into treating pruritus.
Article
Medicine, Research & Experimental
Xueming Hu, Lixia Du, Shenbin Liu, Zhou Lan, Kaikai Zang, Jing Feng, Yonghui Zhao, Xingliang Yang, Zili Xie, Peter L. Wang, Aaron M. Ver Heul, Lvyi Chen, Vijay K. Samineni, Yan-Qing Wang, Kory J. Lavine, Robert W. Gereau Iv, Gregory F. Wu, Hongzhen Hu
Summary: The study found that genetic ablation or pharmacological blockade of TRPV4 significantly reduced neuropathic pain-like behaviors in a mouse model of nerve injury. It was discovered that microglia-expressed TRPV4 mediated microglial activation and proliferation, and promoted functional and structural plasticity of excitatory spinal neurons through the release of lipocalin-2. This identifies TRPV4 as a potential new target for the treatment of chronic pain.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Dermatology
A. M. Trier, M. R. Mack, J. Guo, M. Tamari, A. Fredman, L. K. Oetjen, J. Feng, R. W. Gereau, S. Davidson, H. Hu, Q. Liu, B. S. Kim
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
