BCL6 mediates the effects of Gastrodin on promoting M2-like macrophage polarization and protecting against oxidative stress-induced apoptosis and cell death in macrophages.
Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip®PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients.
School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Jing
J
Jia
Department of Rehabilitation, Shanxi Cerebral Palsy Rehabilitation Hospital, Taiyuan 030006, China.
Xiaojie
X
Shi
Department of Rehabilitation, Shanxi Cerebral Palsy Rehabilitation Hospital, Taiyuan 030006, China.
Xiaoqian
X
Jing
Drug Safety Evaluation Center, China Institute for Radiation Protection, Taiyuan 030006, China.
Jianguo
J
Li
Drug Safety Evaluation Center, China Institute for Radiation Protection, Taiyuan 030006, China.
Jie
J
Gao
Drug Safety Evaluation Center, China Institute for Radiation Protection, Taiyuan 030006, China.
Mengya
M
Liu
Department of Rehabilitation, Shanxi Cerebral Palsy Rehabilitation Hospital, Taiyuan 030006, China.
Chi-Iou
CI
Lin
Department of Rehabilitation, Shanxi Cerebral Palsy Rehabilitation Hospital, Taiyuan 030006, China.
Xinzhi
X
Guo
School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: q.hua07@gmail.com.
Qian
Q
Hua
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001592:Benzyl Alcohols / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002547:Cerebral Palsy / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007223:Infant; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction
D000975:Antioxidants; C490010:Bcl6 protein, mouse; D001592:Benzyl Alcohols; D015415:Biomarkers; D005960:Glucosides; D037181:Lectins, C-Type; C464940:MGL2 protein, mouse; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C045345:gastrodin; D006861:Hydrogen Peroxide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D001119:Arginase
BCL6; Cerebral palsy; Gastrodin; Macrophage polarization