کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8840651 | 1614692 | 2018 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Suppression of Pax2 Attenuates Allodynia and Hyperalgesia through ET-1-ETAR-NFAT5 Signaling in a Rat Model of Neuropathic Pain
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کلمات کلیدی
NF-κBnuclear factor of activated T-cells 5NFAT5paired box gene 2PSNLendothelin receptor type BETARPax2EtBrET-1PWTMAPK - MAPKSAL - WILLendothelin-1 - اندوتلین-1Scramble - تقلاNeuropathic pain - درد نوروپاتیکSaline - سالینNuclear factor-kappa B - فاکتور هسته ای-کاپا Bfluorescence in situ hybridization - فلورسانس در هیبریداسیون در محلFish - ماهیPartial sciatic nerve ligation - پیوند عصب سیاتیک جزئیmitogen-activated protein kinases - کیناز پروتئین فعال Mitogenendothelin receptor type A - گیرنده آندوتلین نوع Aendothelin type A receptor - گیرنده ی نوع آندوتلینSCR - یکسوساز کنترلشده با سیلیکون
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1-ETAR-NFAT5 is a novel regulatory mechanism underlying neuropathic pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 384, 1 August 2018, Pages 139-151
Journal: Neuroscience - Volume 384, 1 August 2018, Pages 139-151
نویسندگان
Lydia Wai Tai, Zhiqiang Pan, Liting Sun, Haobo Li, Pan Gu, Stanley Sau Ching Wong, Sookja K. Chung, Chi Wai Cheung,