Inhibition of CK2 Diminishes Fibrotic Scar Formation and Improves Outcomes After Ischemic Stroke via Reducing BRD4 Phosphorylation

作者全名："Li, Xuemei; Yang, Qinghuan; Jiang, Peiran; Wen, Jun; Chen, Yue; Huang, Jiagui; Tian, Mingfen; Ren, Jiangxia; Yang, Qin"

作者地址："[Li, Xuemei; Yang, Qinghuan; Jiang, Peiran; Wen, Jun; Chen, Yue; Huang, Jiagui; Tian, Mingfen; Ren, Jiangxia; Yang, Qin] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Li, Xuemei] Second Peoples Hosp Chongqing Banan Dist, Dept Neurol, Chongqing, Peoples R China"

通信作者："Yang, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001168331700001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：CK2; p-BRD4; Fibroblast; Fibrotic scar formation; Cerebral ischemia

摘要："Fibrotic scars play important roles in tissue reconstruction and functional recovery in the late stage of nervous system injury. However, the mechanisms underlying fibrotic scar formation and regulation remain unclear. Casein kinase II (CK2) is a protein kinase that regulates a variety of cellular functions through the phosphorylation of proteins, including bromodomain-containing protein 4 (BRD4). CK2 and BRD4 participate in fibrosis formation in a variety of tissues. However, whether CK2 affects fibrotic scar formation remains unclear, as do the mechanisms of signal regulation after cerebral ischemic injury. In this study, we assessed whether CK2 could modulate fibrotic scar formation after cerebral ischemic injury through BRD4. Primary meningeal fibroblasts were isolated from neonatal rats and treated with transforming growth factor-beta 1 (TGF-beta 1), SB431542 (a TGF-beta 1 receptor kinase inhibitor) or TBB (a highly potent CK2 inhibitor). Adult SD rats were intraperitoneally injected with TBB to inhibit CK2 after MCAO/R. We found that CK2 expression was increased in vitro in the TGF-beta 1-induced fibrosis model and in vivo in the MCAO/R injury model. The TGF-beta 1 receptor kinase inhibitor SB431542 decreased CK2 expression in fibroblasts. The CK2 inhibitor TBB reduced the increases in proliferation, migration and activation of fibroblasts caused by TGF-beta 1 in vitro, and it inhibited fibrotic scar formation, ameliorated histopathological damage, protected Nissl bodies, decreased infarct volume and alleviated neurological deficits after MCAO/R injury in vivo. Furthermore, CK2 inhibition decreased BRD4 phosphorylation both in vitro and in vivo. The findings of the present study suggested that CK2 may control BRD4 phosphorylation to regulate fibrotic scar formation, to affecting outcomes after ischemic stroke."

基金机构："the National Natural Science Foundation of China [82171456, 81971229]; National Natural Science Foundation of China [CSTB2023NSCQ-MSX1015]; Natural Science Foundation of Chongqing"

基金资助正文：This project was supported by grants from the National Natural Science Foundation of China (Grant Nos. 82171456 and 81971229) and the Natural Science Foundation of Chongqing (Grant No. CSTB2023NSCQ-MSX1015).