Nppb Neurons Are Sensors of Mast Cell-Induced Itch
CELL REPORTS
Authors: Solinski, Hans Jurgen; Kriegbaum, Mette C.; Tseng, Pang-Yen; Eamest, Thomas W.; Gu, Xinglong; Barik, Arnab; Chesler, Alexander T.; Hoon, Mark A.
Abstract
Itch is an unpleasant skin sensation that can be triggered by exposure to many chemicals, including those released by mast cells. The natriuretic polypeptide b (Nppb)-expressing class of sensory neurons, when activated, elicits scratching responses in mice, but it is unclear which itch-inducing agents stimulate these cells and the receptors involved. Here, we identify receptors expressed by Nppb neurons and demonstrate the functional importance of these receptors as sensors of endogenous pruritogens released by mast cells. Our search for receptors in Nppb neurons reveals that they express leukotriene, serotonin, and sphingosine-1-phosphate receptors. Targeted cell ablation, calcium imaging of primary sensory neurons, and conditional receptor knockout studies demonstrate that these receptors induce itch by the direct stimulation of Nppb neurons and neurotransmission through the canonical gastrin-releasing peptide (GRP)-dependent spinal cord itch pathway. Together, our results define a molecular and cellular pathway for mast cell-induced itch.
ndufa7plays a critical role in cardiac hypertrophy
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Authors: Shi, Xingjuan; Zhang, Yu; Chen, Ru; Gong, Yijie; Zhang, Mingming; Guan, Rui; Rotstein, Ori D.; Liu, Xiangdong; Wen, Xiao-Yan
Abstract
Cardiac hypertrophy is a common pathological change in patients with progressive cardiac function failure, which can be caused by hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arterial hypertension. Despite years of study, there is still limited knowledge about the underlying molecular mechanisms for cardiac hypertrophy. NDUFA7, a subunit of NADH:ubiquinone oxidoreductase (complex I), has been reported to be a novel HCM associated gene. However, the biological role of NDUFA7 in heart remains unknown. In this study, we found that NDUFA7 exhibited high expression in the heart, and its level was significantly decreased in mice model of cardiac hypertrophy. Moreover, we demonstrated thatndufa7knockdown in developing zebrafish embryos resulted in cardiac development and functional defects, associated with increased expression of pathological hypertrophy biomarkers nppa (ANP) and nppb (BNP). Mechanistic study demonstrated thatndufa7depletion promoted ROS production and calcineurin signalling activation. Moreover, NDUFA7 depletion contributed to cardiac cell hypertrophy. Together, these results report for the first time thatndufa7is implicated in pathological cardiac hypertrophy.