Promoting AMPK/SR-A1-mediated clearance of HMGB1 attenuates chemotherapy-induced peripheral neuropathy.
Promoting AMPK/SR-A1-mediated clearance of HMGB1 attenuates chemotherapy-induced peripheral neuropathy.
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DOI：
10.1186/s12964-023-01100-9
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发表时间：
2023-05-04
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影响因子：
--
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Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of chemotherapy with poorly understood mechanisms and few treatments. High-mobility group box 1 (HMGB1)-induced neuroinflammation is the main cause of CIPN. Here, we aimed to illustrate the role of the macrophage scavenger receptor A1 (SR-A1) in HMGB1 clearance and CIPN resolution. Oxaliplatin (L-OHP) was used to establish a CIPN model. Recombinant HMGB1 (rHMGB1) (his tag) was used to evaluate the phagocytosis of HMGB1 by macrophages. In the clinic, HMGB1 expression and MMP-9 activity were increased in the plasma of patients with CIPN. Plasma HMGB1 expression was positively correlated with the cumulative dose of L-OHP and the visual analog scale. In vitro, engulfment and degradation of rHMGB1 increased and inflammatory factor expression decreased after AMP-activated protein kinase (AMPK) activation. Neutralizing antibodies, inhibitors, or knockout of SR-A1 abolished the effects of AMPK activation on rHMGB1 engulfment. In vivo, AMPK activation increased SR-A1 expression in the dorsal root ganglion, decreased plasma HMGB1 expression and MMP-9 activity, and attenuated CIPN, which was abolished by AMPK inhibition or SR-A1 knockout in the CIPN mice model. Activation of the AMPK/SR-A1 axis alleviated CIPN by increasing macrophage-mediated HMGB1 engulfment and degradation. Therefore, promoting HMGB1 clearance may be a potential treatment strategy for CIPN. Video abstract The online version contains supplementary material available at 10.1186/s12964-023-01100-9.
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影响因子：
8.8
作者：
Das N;Dewan V;Grace PM;Gunn RJ;Tamura R;Tzarum N;Watkins LR;Wilson IA;Yin H
通讯作者：
Yin H
影响因子：
1.3
作者：
Bondad, Nazanin;Boostani, Reza;Allahyari, Abolghasem
通讯作者：
Allahyari, Abolghasem
影响因子：
20.3
作者：
Chiang N;Sakuma M;Rodriguez AR;Spur BW;Irimia D;Serhan CN
通讯作者：
Serhan CN
DOI：
10.1096/fj.202002136r
发表时间：
2020-12
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Prantner D;Nallar S;Vogel SN
通讯作者：
Vogel SN
影响因子：
45.3
作者：
Loprinzi, Charles L.;Lacchetti, Christina;Hershman, Dawn L.
通讯作者：
Hershman, Dawn L.