Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren's syndrome condition.
Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren's syndrome condition.
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DOI：
10.1080/08916934.2020.1768376
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发表时间：
2020-08
期刊：
影响因子：
3.5
通讯作者：
Mishra BB
中科院分区：
文献类型：
--
作者：
Singh BB;Ohm J;Quenum Zanbede FO;Chauhan P;Kroese FGM;Vissink A;Ambrus JL;Mishra BB
原发性干燥综合征（pSS）是一种以免疫细胞浸润为特征的全身性自身免疫性疾病。虽然唾液腺功能丧失是pSS的主要表现，但促进pSS唾液腺组织这些变化的因素尚未确定。在此，我们提供的证据表明，α-1抗蛋白酶抗胰蛋白酶的损失可能有助于诱导pSS。α-1抗蛋白酶抗胰蛋白酶属于丝氨酸蛋白酶抑制剂蛋白家族，其作为蛋白酶抑制剂起作用并保护分泌细胞免受蛋白酶，特别是从淋巴细胞分泌的弹性蛋白酶的影响。重要的是，与年龄匹配的非SS-SICCA患者相比，pSS样本中α-1抗蛋白酶抗胰蛋白酶的表达降低（超过3倍），沿着弹性蛋白酶表达增加。与人类数据一致，在表现出SS样症状的IL 14 α转基因小鼠中观察到α-1抗蛋白酶抗胰蛋白酶的丧失以及免疫浸润的增加。此外，在IL 14 α转基因小鼠中观察到弹性蛋白酶表达的年龄依赖性增加沿着总唾液分泌的减少。重要的是，在pSS中观察到microRNA 132表达增加4倍，而不是其他microRNA，以及serpina基因启动子/非编码区的DNA甲基化增加，这可能是pSS患者唾液腺细胞中α-1抗蛋白酶抗胰蛋白酶表达抑制的原因。总之，这些研究结果表明，表观遗传调控，包括DNA甲基化和microRNA，可以调节唾液腺中的α-1抗蛋白酶抗胰蛋白酶的表达，并可能参与pSS的发病。
Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells. Although the loss of salivary gland function is a major manifestation observed in pSS, the factors that could promote these changes in salivary gland tissue in pSS is not yet determined. Herein, we provide evidence that loss of alpha-1 antiproteinase antitrypsin could contribute to the induction of pSS. Alpha-1 antiproteinase antitrypsin belongs to the family of serpin proteins that function as protease inhibitors and protect secretory cells against proteases, especially to elastases that is secreted from lymphocytes. Importantly, expression of alpha-1 antiproteinase antitrypsin was decreased (more than 3-fold), along with an increase in elastase expression, in pSS samples when compared with age-matched non-SS-SICCA patients. Consistent with the human data, loss of alpha-1 antiproteinase antitrypsin, as well as an increase in immune infiltration, was observed in IL14α transgenic mice that exhibit SS like symptoms. Moreover, an age-dependent increase in elastase expression was observed in IL14α transgenic mice along with a decrease in total saliva secretion. Importantly, a 4-fold increase in microRNA132 expression, but not in other microRNAs, and increased DNA methylation in the promoter/noncoding region of serpina gene was observed in pSS, which could be responsible for the inhibition of alpha-1 antiproteinase antitrypsin expression in salivary gland cells of pSS patients. Together, these findings demonstrate that epigenetic regulations that include DNA methylation and microRNAs that could modulate the expression of alpha-1 antiproteinase antitrypsin in salivary glands and could be involved in the onset of pSS.
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影响因子：
9
作者：
Huber-Lang M;Ekdahl KN;Wiegner R;Fromell K;Nilsson B
通讯作者：
Nilsson B
影响因子：
5
作者：
Churg, A;Dai, J;Wright, JL
通讯作者：
Wright, JL
影响因子：
3.5
作者：
Leehan KM;Pezant NP;Rasmussen A;Grundahl K;Moore JS;Radfar L;Lewis DM;Stone DU;Lessard CJ;Rhodus NL;Segal BM;Kaufman CE;Scofield RH;Sivils KL;Montgomery C;Farris AD
通讯作者：
Farris AD
影响因子：
37.8
作者：
Daemen, MARC;Heemskerk, VH;Buurman, WA
通讯作者：
Buurman, WA
影响因子：
4.8
作者：
Krem, MM;Di Cera, E
通讯作者：
Di Cera, E