Secreted Protein Acidic and Cysteine Rich (SPARC) Regulates the Pathological Response to Ischemic Insults and Represents a Promising Therapeutic Target for Stroke Treatment

Zhou, Yu1,2,3; Peng, Jing4; Cheng, Lamei4; Peng, Yong3; Zhang, Mingming3; Liu, Min3; Avery, Jonathan2; Zhou, Jiangbing2; Jiang, Yugang3

2019-10

10.1002/adtp.201900082

Advanced Therapeutics   影响因子和分区

2366-3987

2366-3987

Secreted protein acidic and cysteine rich (SPARC) is a nonstructural, multifunctional matricellular protein involved in tissue development, extracellular matrix, and immune response. In this study, by using mice deficient in SPARC, the role of SPARC in the pathogenesis of ischemic stroke is characterized. It is found that, compared to the wild-type mice, SPARC deficient mice demonstrated 48.3% reduction in cerebral infarction after ischemia insult. Mechanistically, it is shown that SPARC deficiency significantly reduces ischemia induced cellular apoptosis, diminishes inflammatory response in the ischemic area as well as in the circulatory system, and enhances the integrity of the blood-brain barrier. It is further assessed if SPARC could be targeted for stroke treatment through intraventricular or intravenous administration of SPARC neutralizing antibody. It is found that delivery of SPARC antibody through either route effectively reduces ischemia-induced infarction. Taken together, the study suggests that SPARC plays an important role in the pathological response to ischemic insults, and represents a promising therapeutic target for clinical management of stroke.

immune response ischemic stroke middle cerebral artery occlusion secreted protein acidic and cysteine rich therapeutic target

ESCI

英语

第一

American Heart Association[18TPA34170180][19CSLOI3477000] ; National High Technology Research and Development Program of China[2011AA020113] ; National Natural Science Foundation of China[81460244]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:000506360500008

WILEY

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Neurosurg, Shenzhen 518020, Guangdong, Peoples R China
2.Yale Univ, Dept Neurosurg, New Haven, CT 06511 USA
3.Cent S Univ, Xiangya Hosp 2, Dept Neurosurg, Changsha 410000, Hunan, Peoples R China
4.Cent S Univ, Natl Engn Res Ctr Human Stem Cells, Changsha 410000, Hunan, Peoples R China

Zhou, Yu,Peng, Jing,Cheng, Lamei,et al. Secreted Protein Acidic and Cysteine Rich (SPARC) Regulates the Pathological Response to Ischemic Insults and Represents a Promising Therapeutic Target for Stroke Treatment[J]. Advanced Therapeutics,2019,2(10).

Zhou, Yu.,Peng, Jing.,Cheng, Lamei.,Peng, Yong.,Zhang, Mingming.,...&Jiang, Yugang.(2019).Secreted Protein Acidic and Cysteine Rich (SPARC) Regulates the Pathological Response to Ischemic Insults and Represents a Promising Therapeutic Target for Stroke Treatment.Advanced Therapeutics,2(10).

Zhou, Yu,et al."Secreted Protein Acidic and Cysteine Rich (SPARC) Regulates the Pathological Response to Ischemic Insults and Represents a Promising Therapeutic Target for Stroke Treatment".Advanced Therapeutics 2.10(2019).