QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation
Si-Yi Xu,
Jun-Qiu Jia,
Min Sun,
Xin-Yu Bao,
Sheng-Nan Xia,
Shu Shu,
Pin-yi Liu,
Sen-lin Ji,
Lei Ye,
Xiang Cao,
Yun Xu
Affiliations
Si-Yi Xu
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Jun-Qiu Jia
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Min Sun
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Xin-Yu Bao
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China
Sheng-Nan Xia
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China
Shu Shu
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China
Pin-yi Liu
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China
Sen-lin Ji
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China
Lei Ye
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Xiang Cao
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China; Corresponding author
Yun Xu
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China; Corresponding author
Summary: Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effect of QHRD106 in ischemic stroke and its possible mechanism. We found that QHRD106 treatment alleviated brain injury after stroke via bradykinin (BK) receptor B2 (B2R) instead of BK receptor B1 (B1R). Mechanistically, QHRD106 reduced high-mobility group box 1 (HMGB1)-induced apoptosis and inflammation after ischemic stroke in vivo and in vitro. Moreover, we confirmed that QHRD106 reduced the level of acetylated HMGB1 and reduced the binding between heat shock protein 90 alpha family class A member 1 (HSP90AA1) and HMGB1, thus inhibiting the translocation and release of HMGB1. In summary, these findings indicate that QHRD106 treatment has therapeutic potential for cerebral ischemic stroke.
