PRKAR2A deficiency protects mice from experimental colitis by increasing IFN-stimulated gene expression and modulating the intestinal microbiota.
PRKAR2A deficiency protects mice from experimental colitis by increasing IFN-stimulated gene expression and modulating the intestinal microbiota.
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PRKAR2A 缺陷通过增加 IFN 刺激的基因表达和调节肠道微生物群来保护小鼠免受实验性结肠炎
DOI：
10.1038/s41385-021-00426-2
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发表时间：
2021-11
影响因子：
8
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Wei L;Zhang R;Zhang J;Li J;Kong D;Wang Q;Fang J;Wang L
摘要蛋白激酶A（PKA）通过其催化亚基在炎症调节中起重要作用。近年来，PKA调节亚基被报道可以直接调节某些信号通路，减轻炎症反应。然而，PKA调节亚基在结肠炎症中的作用仍不清楚。因此，我们进行了这项研究来探讨PKA调节亚基PRKAR 2A在结肠炎中的作用。我们观察到PRKAR 2A缺陷保护小鼠免受葡聚糖硫酸钠（DSS）诱导的实验性结肠炎。我们的实验表明，肠上皮细胞特异性Prkar 2a缺失有助于这种保护。从机制上讲，Prkar 2a −/−小鼠中PRKAR 2A的缺失导致IFN刺激基因（ISG）表达增加和肠道微生物群改变。抑制ISG部分逆转了Prkar 2a −/−小鼠对DSS诱导的结肠炎的保护作用。抗生素治疗和交叉培养实验表明，Prkar 2a −/−小鼠对DSS诱导的结肠炎的保护在很大程度上取决于肠道微生物菌群。总之，我们的工作证明了PRKAR 2A在促进DSS诱导的结肠炎中的先前未鉴定的功能。
Abstract Protein kinase A (PKA) plays an important role in regulating inflammation via its catalytic subunits. Recently, PKA regulatory subunits have been reported to directly modulate some signaling pathways and alleviate inflammation. However, the role of PKA regulatory subunits in colonic inflammation remains unclear. Therefore, we conducted this study to investigate the role of the PKA regulatory subunit PRKAR2A in colitis. We observed that PRKAR2A deficiency protected mice from dextran sulfate sodium (DSS)-induced experimental colitis. Our experiments revealed that the intestinal epithelial cell-specific deletion of Prkar2a contributed to this protection. Mechanistically, the loss of PRKAR2A in Prkar2a −/− mice resulted in an increased IFN-stimulated gene (ISG) expression and altered gut microbiota. Inhibition of ISGs partially reversed the protective effects against DSS-induced colitis in Prkar2a −/− mice. Antibiotic treatment and cross-fostering experiments demonstrated that the protection against DSS-induced colitis in Prkar2a −/− mice was largely dependent on the gut microflora. Altogether, our work demonstrates a previously unidentified function of PRKAR2A in promoting DSS-induced colitis.
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影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
11.1
作者：
Li J;Kong D;Wang Q;Wu W;Tang Y;Bai T;Guo L;Wei L;Zhang Q;Yu Y;Qian Y;Zuo S;Liu G;Liu Q;Wu S;Zang Y;Zhu Q;Jia D;Wang Y;Yao W;Ji Y;Yin H;Nakamura M;Lazarus M;Breyer RM;Wang L;Yu Y
通讯作者：
Yu Y
DOI：
10.1073/pnas.0400567101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Chang, HM;Paulson, M;Levy, DE
通讯作者：
Levy, DE
DOI：
10.1073/pnas.94.20.11067
发表时间：
1997-09-30
影响因子：
11.1
作者：
Burton, KA;Johnson, BD;McKnight, GS
通讯作者：
McKnight, GS
影响因子：
29.4
作者：
Chiriac, Mircea T.;Buchen, Barbara;Neurath, Markus F.
通讯作者：
Neurath, Markus F.