EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D

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	EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D
	Luo, Yonglun 1,3; Tian, Weiping 1; Cai, Lun 2; Wang, Yan 1; Zhang, Jing 1; Teng, Huajing 1; Du, Jie 1,2; Sun, Zhong Sheng 1,3; Zhong ShengSun
摘要	The mammalian circadian gene, mPer2, an indispensable component of the mammalian circadian clock, not only modulates endogenous circadian rhythms but also plays a crucial role in regulating innate immune function. Previously, we showed that mPer2 plays a crucial role in regulating cytotoxic response. To investigate the molecular mechanism for mPer2-controlled cytotoxic response, in the present study we conducted mRNA expression for 11 genes participating in cytotoxicity regulation in wild-type (WT) and mPer2 knockout (mPer2 −; ; / −; ; ) mice bone marrow, that is, Dap-10, Ly49C, Ly49I, Rac1, Mapk1, Map2k1, Nkg2d, Shp-1, Pak1, Pik3ca, and Vav1. The mRNA levels of Ly49C (p < 0.001), Ly49I (p = 0.039), and Nkg2d (p = 0.038) were significantly downregulated in mPer2 −; ; / −; ; mice. Time-dependence of expression profiling was then conducted for four core clock genes (Per1, Bmal1, Clock, Rev-erbα), and six out of these 11 cytotoxic regulation genes (Ly49C, Ly49I, Mapk1, Nkg2d, Shp-1, Pik3ca) in WT and mPer2 −; ; / −; ; entrained in light/dark (LD) or dark/dark (DD) cycles. Consistently, circadian oscillations were observed for Per1, Rev-erbα, Ly49C, and Nkg2d in WT mice under LD and DD cycles. However, these rhythmic expressions were either disrupted or dampened in mPer2 −; ; / −; ; mice. Comparison of gene expression between WT and mPer2 −; ; / −; ; mice showed that mPer2 knockout had systematically downregulated the mRNA expression of two cytotoxicity regulators, Ly49C and Nkg2d. FACS analysis further confirmed that the circadian expression of these genes was not due to the daily difference in cell numbers of NK, NKT, or T cells in bone marrow. Taken together, our results reveal that mPer2 is a critical clock component in modulating circadian rhythms in bone marrow. Furthermore, it implies that Ly49C and Nkg2d are two clock-controlled genes that may play an important role in mediating mPer2-controlled cytotoxic response.; The mammalian circadian gene, mPer2, an indispensable component of the mammalian circadian clock, not only modulates endogenous circadian rhythms but also plays a crucial role in regulating innate immune function. Previously, we showed that mPer2 plays a crucial role in regulating cytotoxic response. To investigate the molecular mechanism for mPer2-controlled cytotoxic response, in the present study we conducted mRNA expression for 11 genes participating in cytotoxicity regulation in wild-type (WT) and mPer2 knockout (mPer2(-/-)) mice bone marrow, that is, Dap-10, Ly49C, Ly49I Rac1, Mapk1, Map2k1, Nkg2d, Shp-1, Pak1, Pik3ca, and Vav1. The mRNA levels of Ly49C (p < 0.001), Ly49I (p = 0.039), and Nkg2d (p = 0.038) were significantly downregulated in mPer2(-/-) mice. Time-dependence of expression profiling was then conducted for four core clock genes (Per1, Bmal1, Clock, Rev-erb alpha), and six out of these 11 cytotoxic regulation genes (Ly49C, Ly49I, Mapk1, Nkg2d, Shp-1, Pik3ca) in WT and mPer2(-/-) entrained in light/dark (LD) or dark/dark (DD) cycles. Consistently, circadian oscillations were observed for Per1, Rev-erb alpha, Ly49C, and Nkg2d in WT mice under LD and DD cycles. However, these rhythmic expressions were either disrupted or dampened in mPer2(-/-) mice. Comparison of gene expression between WT and mPer2(-/-) mice showed that mPer2 knockout had systematically downregulated the mRNA expression of two cytotoxicity regulators, Ly49C and Nkg2d. FACS analysis further confirmed that the circadian expression of these genes was not due to the daily difference in cell numbers of NK, NKT, or T cells in bone marrow. Taken together, our results reveal that mPer2 is a critical clock component in modulating circadian rhythms in bone marrow. Furthermore, it implies that Ly49C and Nkg2d are two clock-controlled genes that may play an important role in mediating mPer2-controlled cytotoxic response. (Author correspondence: zsunusa@yahoo.com)
关键词	Cytotoxicity regulation Cytotoxicity receptors mPer2 Ly49C Nkg2d
学科领域	遗传学
	2009
语种	英语
发表期刊	CHRONOBIOLOGY INTERNATIONAL
ISSN	0742-0528
卷号	26 期号:8 页码:1514-1544
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000279983800002
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://ir.psych.ac.cn/handle/311026/5405
专题	中国科学院心理研究所回溯数据库(1956-2010)
通讯作者	Zhong ShengSun
作者单位	1.Chinese Acad Sci, Behav Genet Ctr, Inst Psychol, Beijing 101300, Peoples R China 2.Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R China 3.Chinese Acad Sci, Grad Univ, Beijing 101300, Peoples R China
推荐引用方式 GB/T 7714	Luo, Yonglun,Tian, Weiping,Cai, Lun,et al. EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D[J]. CHRONOBIOLOGY INTERNATIONAL,2009,26(8):1514-1544.
APA	Luo, Yonglun.,Tian, Weiping.,Cai, Lun.,Wang, Yan.,Zhang, Jing.,...&Zhong ShengSun.(2009).EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D.CHRONOBIOLOGY INTERNATIONAL,26(8),1514-1544.
MLA	Luo, Yonglun,et al."EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D".CHRONOBIOLOGY INTERNATIONAL 26.8(2009):1514-1544.

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