Identification of histone deacetylase inhibitors as neutrophil recruitment modulators in zebrafish using a chemical library screen

作者全名："Fan, Sijia; Jiang, Jinlong; Zhang, Huan; Wang, Cuihong; Kong, Shang; Zhao, Tingting; Meng, Ling; Liu, Yang; Qin, Jingjing; Rong, Xiuqin; He, Zhenting; He, Qinke; He, Ke; Chen, Ketong; Lei, Ling; Hai, Xinyu; Nie, Hong; Ren, Chunguang"

作者地址："[Fan, Sijia; Jiang, Jinlong; Zhang, Huan; Wang, Cuihong; Meng, Ling; Liu, Yang; Qin, Jingjing; Rong, Xiuqin; He, Zhenting; He, Qinke; He, Ke; Chen, Ketong; Lei, Ling; Hai, Xinyu; Ren, Chunguang] Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China; [Kong, Shang; Zhao, Tingting; Nie, Hong] Jinan Univ, Coll Pharm, Int Cooperat Lab Tradit Chinese Med Modernizat & I, Chinese Minist Educ MOE, Guangzhou 510632, Peoples R China; [Kong, Shang; Zhao, Tingting; Nie, Hong] Jinan Univ, Coll Pharm, Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Peoples R China"

通信作者："Ren, CG (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Cell Biol & Genet, Lab Dev Biol, Chongqing 400016, Peoples R China.; Nie, H (通讯作者)，Jinan Univ, Coll Pharm, Int Cooperat Lab Tradit Chinese Med Modernizat & I, Chinese Minist Educ MOE, Guangzhou 510632, Peoples R China.; Nie, H (通讯作者)，Jinan Univ, Coll Pharm, Guangdong Prov Key Lab Pharmacodynam Constituents, Guangzhou 510632, Peoples R China."

来源：DISEASE MODELS & MECHANISMS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001106876100004

JCR分区：Q1

影响因子：4

年份：2023

卷号：16

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：Zebrafish; Neutrophil; Cell migration; HDAC; AR-42

摘要："Tissue injury-induced neutrophil recruitment is a prerequisite for the initiation and amplification of inflammatory responses. Although multiple proteases and enzymes involved in post-translational modification (PTM) of proteins regulate leukocyte recruitment, an unbiased functional screen of enzymes regulating inflammatory leukocyte recruitment has yet to be undertaken. Here, using a zebrafish tail fin amputation (TFA) model to screen a chemical library consisting of 295 compounds that target proteases and PTM a pan-HDAC inhibitor, was shown to inhibit neutrophil recruitment in three different zebrafish sterile tissue injury models: a TFA model, a copper-induced neuromast damage and mechanical otic vesicle injury (MOVI) model, and a sterile murine peritonitis model. RNA sequencing analysis of AR-42-treated fish embryos revealed downregulation of neutrophil-associated cytokines/chemokines, and exogenous supplementation with recombinant human IL-1 beta and CXCL8 partially restored the defective neutrophil recruitment in AR-42-treated MOVI model fish embryos. We thus demonstrate that AR-42 non-cell-autonomously modulates neutrophil recruitment by suppressing transcriptional expression of cytokines/chemokines, thereby identifying AR-42 as a promising anti-inflammatory drug for treating sterile tissue injury-associated diseases."

基金机构："National Natural Science Foundation of China [32170766, 8181101216]; China Postdoctoral Science Foundation [2021MD703921]; Chongqing Municipal Science and Technology Bureau [CSTB2022BSXM-JCX0036, cstc2021jcyj-bshX0080]; Chongqing Municipal Human Resources and Social Security Bureau [cx2020029]; Program for Youth Innovation in Future Medicine (Chongqing Medical University) [W0052]; Chongqing Medical University"

基金资助正文："This study was supported by National Natural Science Foundation of China (grant nos. 32170766 and 8181101216) , China Postdoctoral Science Foundation (grant no. 2021MD703921) , Chongqing Municipal Science and Technology Bureau (grant nos. CSTB2022BSXM-JCX0036 and cstc2021jcyj-bshX0080) , Chongqing Municipal Human Resources and Social Security Bureau (grant no. cx2020029) and Program for Youth Innovation in Future Medicine (Chongqing Medical University; grant no. W0052) . Open Access funding provided by Chongqing Medical University. Deposited in PMC for immediate release."