Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting

Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present.Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed....

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Autores principales:	Lu Li, Huiquan Liu, Weili Tao, Su Wen, Xiaofen Fu, Shiying Yu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HMGB1 cancer cachexia skeletal muscle NF-κB TLR4 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/deeb4634bf0f4d1c9c8eb478e81f3f2e
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spelling	oai:doaj.org-article:deeb4634bf0f4d1c9c8eb478e81f3f2e2021-11-18T09:54:18ZPharmacological Inhibition of HMGB1 Prevents Muscle Wasting1663-981210.3389/fphar.2021.731386https://doaj.org/article/deeb4634bf0f4d1c9c8eb478e81f3f2e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.731386/fullhttps://doaj.org/toc/1663-9812Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present.Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model.Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo.Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.Lu LiHuiquan LiuWeili TaoSu WenXiaofen FuShiying YuFrontiers Media S.A.articleHMGB1cancer cachexiaskeletal muscleNF-κBTLR4Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HMGB1 cancer cachexia skeletal muscle NF-κB TLR4 Therapeutics. Pharmacology RM1-950
spellingShingle	HMGB1 cancer cachexia skeletal muscle NF-κB TLR4 Therapeutics. Pharmacology RM1-950 Lu Li Huiquan Liu Weili Tao Su Wen Xiaofen Fu Shiying Yu Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
description	Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present.Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model.Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo.Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.
format	article
author	Lu Li Huiquan Liu Weili Tao Su Wen Xiaofen Fu Shiying Yu
author_facet	Lu Li Huiquan Liu Weili Tao Su Wen Xiaofen Fu Shiying Yu
author_sort	Lu Li
title	Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
title_short	Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
title_full	Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
title_fullStr	Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
title_full_unstemmed	Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting
title_sort	pharmacological inhibition of hmgb1 prevents muscle wasting
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/deeb4634bf0f4d1c9c8eb478e81f3f2e
work_keys_str_mv	AT luli pharmacologicalinhibitionofhmgb1preventsmusclewasting AT huiquanliu pharmacologicalinhibitionofhmgb1preventsmusclewasting AT weilitao pharmacologicalinhibitionofhmgb1preventsmusclewasting AT suwen pharmacologicalinhibitionofhmgb1preventsmusclewasting AT xiaofenfu pharmacologicalinhibitionofhmgb1preventsmusclewasting AT shiyingyu pharmacologicalinhibitionofhmgb1preventsmusclewasting
_version_	1718420875997347840

Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting

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