title: High-mobility group box 1 released from astrocytes promotes the proliferation of cultured neural stem/progenitor cells.
abstract: Astrocytes are major components of the adult neurogenic niche and play a crucial role in regulating neural stem cell proliferation and differentiation. Following brain injury, astrocytes become reactive and release high-mobility group box 1 (HMGB1), which plays a crucial role in the inflammatory process. However, although it has been reported that HMGB1 promotes neural stem/progenitor cell (NS/PC) proliferation in the developing brain, whether HMGB1 released by reactive astrocytes regulates NS/PC proliferation remains unknown. In this study, we aimed to investigate whether HMGB1 released from reactive astrocytes enhances NS/PC proliferation and to elucidate the possible mechanisms involved in this process. To evaluate the effects of HMGB1 on NS/PC proliferation, NS/PCs were cultured in HMGB1 culture medium and astrocyte-conditioned medium with or without reactive astrocyte-derived HMGB1 by RNA interference (RNAi). To explore the possible mechanisms, the HMGB1 receptor for advanced glycation endproducts (RAGE) in the NS/PCs was blocked with anti-RAGE antibody, and c-Jun N-terminal protein kinase (JNK) in the NS/PCs was inhibited using the potent JNK inhibitor, SP600125. Our results suggested that HMGB1 released from reactive astrocytes promoted NS/PC proliferation in vitro, and the blockade of RAGE or the inhibition of the JNK signaling pathway in the NS/PCs prevented the HMGB1-induced NS/PC proliferation. Our findings demonstrated that HMGB1 released by reactive astrocytes promoted NS/PC proliferation by binding RAGE and enhancing the phosphorylation of the JNK signaling pathway. These findings support a previously described mechanism of a crosstalk between astrocytes and NS/PCs, and suggest that reactive astrocyte-derived HMGB1 plays an important role in the repair of the central nervous system following brain injury.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 40016, P.R. China.
authors: Man
authors: M
authors: Li
authors: Department of Orthopedics, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi 030032, P.R. China.
authors: Lin
authors: L
authors: Sun
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 40016, P.R. China.
authors: Yong
authors: Y
authors: Luo
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 40016, P.R. China.
authors: Chenchen
authors: C
authors: Xie
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 40016, P.R. China.
authors: Yueshan
authors: Y
authors: Pang
authors: Basic Medicine College of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors: Yuan
authors: Y
authors: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D064231:Nestin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat