The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth.
The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth.
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缓激肽系统有助于调节人羊膜成纤维细胞中前列腺素 - 耐氧化酶合酶2的表达：对术语和早产的影响。
DOI：
10.3389/fendo.2022.873727
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
缓激肽 (BK) 及其生物活性代谢物 des-Arg9 缓激肽 (DABK) 在炎症中发挥着关键作用。由于绒毛膜羊膜炎是早产的主要原因，而源自羊膜的前列腺素 E2 (PGE2) 是分娩开始的关键，因此我们研究了缓激肽肽是否是分娩时人羊膜中 PGE2 合成调节网络的一部分。从足月和早产中获取人羊膜组织，用于研究分娩时缓激肽系统的变化。培养的原代人羊膜成纤维细胞是 PGE2 的主要来源，用于研究缓激肽肽对 PTGS2 表达和 PGE2 产生的影响以及感染介质对缓激肽受体的影响。缓激肽及其受体 BDKRB1 和 BDKRB2 存在于人类羊膜中，并且它们的丰度在足月和早产时增加。然而，尽管足月和早产时缓激肽肽的丰度增加，但在人羊膜中几乎检测不到编码缓激肽前体及其蛋白水解酶的基因转录本，这表明人羊膜存在缓激肽肽的替代来源，并且它们的作用在分娩时的人羊膜中增强。对培养的人羊膜成纤维细胞的体外研究表明，BK 和 DABK 均可增加前列腺素内过氧化物合酶 2 (PTGS2) 的表达，PTGS2 是前列腺素合成和随后的 PGE2 生成的限速酶。 BK 和 DABK 的这些作用分别通过 BDKRB2 和 BDKRB1 受体介导，随后激活 p38 和 ERK1/2 途径。此外，脂多糖（LPS）和血清淀粉样蛋白A1（SAA1）是感染性炎症的重要介质，通过Toll样受体4（TLR4）诱导BDKRB1和BDKRB2的表达。 LPS 和 SAA1 诱导 BDKRB1 和 BDKRB2 表达增强了人羊膜成纤维细胞中 BK 或 DABK 诱导的 PTGS2 表达和 PGE2 产生。这项研究首次证明，人羊膜是缓激肽肽的靶组织，缓激肽系统可能是足月和早产时人羊膜成纤维细胞中PTGS2表达和PGE2产生调节网络的一部分，并且感染可能会增强这一网络。
Bradykinin (BK) and its biologically active metabolite des-Arg9 bradykinin (DABK) play a pivotal role in inflammation. Since chorioamnionitis is the leading cause of preterm birth and prostaglandin E2 (PGE2) derived from the amnion is key to labor initiation, we investigated if bradykinin peptides are part of the regulatory network of PGE2 synthesis in human amnion at parturition. Human amnion tissue was obtained from term and preterm birth for the study of the changes of the bradykinin system at parturition. Cultured primary human amnion fibroblasts, the major source of PGE2, were used to study the effects of bradykinin peptides on PTGS2 expression and PGE2 production as well as the effects of infection mediators on bradykinin receptors. Bradykinin peptides and their receptors BDKRB1 and BDKRB2 were present in human amnion, and their abundance increased in term and preterm labor. However, transcripts of the genes encoding the bradykinin precursor and its proteolytic cleavage enzymes were hardly detectable in human amnion despite the increased abundance of bradykinin peptides in term and preterm labor, suggesting that there is an alternative source of bradykinin peptides for human amnion and their actions are enhanced in human amnion at parturition. In-vitro studies in cultured human amnion fibroblasts showed that both BK and DABK increased the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the rate-limiting enzyme in prostaglandin synthesis, and subsequent PGE2 production. These effects of BK and DABK were mediated through BDKRB2 and BDKRB1 receptors, respectively, with subsequent activation of the p38 and ERK1/2 pathways. Moreover, lipopolysaccharide (LPS) and serum amyloid A1 (SAA1), the important mediators of infectious inflammation, induced the expression of both BDKRB1 and BDKRB2 through toll-like receptor 4 (TLR4). Induction of BDKRB1 and BDKRB2 expression by LPS and SAA1 enhanced BK- or DABK-induced PTGS2 expression and PGE2 production in human amnion fibroblasts. This study demonstrated for the first time that the human amnion is a target tissue of bradykinin peptides and the bradykinin system may be part of the regulatory network of PTGS2 expression and PGE2 production in human amnion fibroblasts at both term and preterm birth, which may be enhanced by infection.
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DOI：
10.1186/s12964-020-00680-0
发表时间：
2020-11-23
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Lee TH;Liu PS;Tsai MM;Chen JL;Wang SJ;Hsieh HL
通讯作者：
Hsieh HL
人羊膜成纤维细胞中血清淀粉样蛋白 A1 诱导促炎基因
影响因子：
4.6
作者：
Li W;Wang W;Zuo R;Liu C;Shu Q;Ying H;Sun K
通讯作者：
Sun K
影响因子：
3.6
作者：
HELLBERG, P;LARSON, L;BRANNSTROM, M
通讯作者：
BRANNSTROM, M
DOI：
10.1016/0304-4165(88)90033-5
发表时间：
1988-03-17
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CHAO, J;SWAIN, C;CHAO, L
通讯作者：
CHAO, L
影响因子：
4
作者：
Lu, Dah-Yuu;Leung, Yuk-Man;Wong, Kar-Lok
通讯作者：
Wong, Kar-Lok