Janus蛋白酪氨酸激酶2/信号转导和转录激活因子3信号转导通路在人慢性根尖周炎中的表达
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摘要
目的:检测Janus蛋白酪氨酸激酶2/信号转导和转录激活子3(Janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)信号转导通路在人慢性根尖周炎中的表达并推测其在慢性根尖周炎中的作用,为研究慢性根尖周病的致病机制提供理论基础。方法:选取健康牙齿牙周膜为对照组,患有根尖周囊肿及根尖周肉芽肿标本分别为实验组1、实验组2,每组各20例,对各组标本分别进行苏木精-伊红(hematoxylin-eosin staining,HE)染色并采用免疫组织化学法检测JAK2、磷酸化Janus蛋白酪氨酸激酶2(phosphorylation-janus kinase 2,p-JAK2)、STAT3及磷酸化信号转导和转录激活子3(phosphorylation-signal transducer and activator of transcription 3,p-STAT3)在各组中的表达。结果:JAK2、p-JAK2、STAT3、p-STAT3在正常牙周组织中均有少量表达,在根尖周囊肿及肉芽肿组织中表达量增加,实验组1、实验组2与对照组比较差异均有统计学意义(P<0.05)。实验组1与实验组2比较,JAK2及p-JAK2的表达差异有统计学意义(P<0.05),STAT3及p-STAT3的表达差异无统计学意义(P>0.05)。对根尖周炎标本中的JAK2和STAT3以及p-JAK2和p-STAT3进行相关性分析,结果显示JAK2和STAT3以及p-JAK2和p-STAT3之间有相关性。结论:JAK2、p-JAK2、STAT3及p-STAT3在慢性根尖周炎中表达量增加,推测JAK2/STAT3信号通路与根尖周炎的炎症过程有关,可能在其发展过程中有重要意义。
Objective:To detect the expression of JAK2/STAT3 signal transduction pathway in chronic apical periodontitis in human and speculate its role in chronic periapical diseases.Methods:Twenty healthy periodontal membranes,20 periapical cysts,and 20 periapical granuloma specimens were stained by HE.Immunohistochemistry was used to detect the expression of JAK2,p-JAK2,STAT3,and p-STAT3 in different groups.Results:JAK2,pJAK2,STAT3,and p-STAT3 were slightly expressed in normal tissues,and increased in periapical cysts and granuloma.The differences were statistically significant(P<0.05).The difference between JAK2 and p-JAK2 was statistically significant(P<0.05).There was no significant difference in STAT3 and p-STAT3 between periapical cyst group and periapical granuloma group(P>0.05).Tere was a correlation between JAK2 and STAT3and p-JAK2 and p-STAT3.Conclusion:The expressions of JAK2,p-JAK2,STAT3,and p-STAT3 were in creased inchronic periapical diseases.We speculate that JAK2/STAT3 signaling pathway is involved in the inflammatory process of periapical perioditis and may play an important role in its development.
Objective:To detect the expression of JAK2/STAT3 signal transduction pathway in chronic apical periodontitis in human and speculate its role in chronic periapical diseases.Methods:Twenty healthy periodontal membranes,20 periapical cysts,and 20 periapical granuloma specimens were stained by HE.Immunohistochemistry was used to detect the expression of JAK2,p-JAK2,STAT3,and p-STAT3 in different groups.Results:JAK2,pJAK2,STAT3,and p-STAT3 were slightly expressed in normal tissues,and increased in periapical cysts and granuloma.The differences were statistically significant(P<0.05).The difference between JAK2 and p-JAK2 was statistically significant(P<0.05).There was no significant difference in STAT3 and p-STAT3 between periapical cyst group and periapical granuloma group(P>0.05).Tere was a correlation between JAK2 and STAT3and p-JAK2 and p-STAT3.Conclusion:The expressions of JAK2,p-JAK2,STAT3,and p-STAT3 were in creased inchronic periapical diseases.We speculate that JAK2/STAT3 signaling pathway is involved in the inflammatory process of periapical perioditis and may play an important role in its development.
引文
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[2]梁又德,周毅,李异雷,等.p-JAK2和p-STAT3在实验性牙移动牙周组织中的表达及意义[J].口腔医学研究,2014,30(8):724-727.
[3]李常虹,赵金霞,孙琳,等.JAK2/STAT3信号通路对RANKL诱导的RAW264.7细胞向破骨细胞分化的影响[J].中国骨质疏松杂志,2013,19(5):421-425.
[4]Stashenko P,Teles R,Souza RD.Periapical inflammatory responses and their modulation[J].Oral Surg Oral Med Oral Pathol Oral Radiol,1998,9(4):498-521.
[5]Zhang R,Wang L,Peng B.Activation of p38mitogen-activated protein kinase in rat periapical lesions[J].J Endod,2008,34(10):1207-1210.
[6]敖翔,王丽娜,王娇娇,等.JAK2-STAT3信号通路在大鼠根尖周炎中表达的相关性研究[J].口腔医学研究,2017,33(1):1-5.
[7]Stashenko P,Teles R,D'Souza R.Periapical inflammatory responses and their modulation[J].Crit Rev Oral Biol Med,1998,9(4):498-521.
[8]Li J,Wang R,Huang SG.Immunomodulatory activity of interleukin-27in human chronic periapical diseases[J].AM JTransl Res,2017,9(3):1460-1470.
[9]Vernal R,Dezerega A,Dutzan N,et al.RANKL in human periapical granuloma:possible involvement in periapical bone destruction[J].Oral Dis,2006,12(3):283-289.
[10]Liu L,Zhang C,Hu Y,et al.Protective effect of metformin on periapical lesions in rats by decreasing the ratio of receptor activator of nuclear factor kappa B ligand/osteoprotegerin[J].J Endod,2012,38(7):943-947.
[11]Gao B,Chen W,Hao L,et al.Inhibiting periapical lesions through AAV-RNAi silencing of cathepsin K[J].J Dent Res,2013,92(2):180-186.
[12]Witthuhn BA,Quelle FW,Silvennoinen O,et al.JAK2associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin[J].Cell,1993,74(2):227-236.
[13]Watling D,Guschin D,Muller M,et al.Complementation by the protein tyrosine kinase JAK2of a mutant cell line defective in the interferon-gamma signal transduction pathway[J].Nature,1993,366(6451):166-170.
[14]Waters MJ,Brooks AJ.JAK2activation by growth hormone and other cytokines[J].Biochem J,2015,466(1):1-11.
[15]Slootweg MC.Growth hormone and bone[J].Horm Metab Res,1993,25(7):335-343.
[16]Agrawal S,Gollapudi S,Su H,et al.Leptin activates human B cells to secrete TNF-alpha,IL-6,and IL-10via JAK2/STAT3and p38MAPK/ERK1/2signaling pathway[J].JClin Immunol,2011,31(3):472-478.
[17]Abroun S,Saki N,Ahmadvand M,et al.STATs:an old story,yet mesmerizing[J].Cell J,2015,17(3):395-411.
[18]O'Brien CA,Gubrij I,Lin SC,et al.STAT3activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1but not 1,25-dihydroxyvitamin D3or parathyroid hormo[J].J Biol Chem,1999,274(27):19301.