Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway

Background: In mammals, skeletal muscle typically constitutes approximately 55% of body weight. The thermogenesis of skeletal muscle increases with increased cold stress, and skeletal muscle maintains the animal’s body temperature through the heat generated by shivering. However,...

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Main Authors: Minxing Zheng, Jiahui Qi, Xuanjing Wang, Tingting Fu, Ziqi Chang, Tong Zhao, Yaqin Sun, Jiayin Lu, Yi Yan, Haidong Wang
Format: Article
Language:English
Published: IMR Press 2025-07-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL40141
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author Minxing Zheng
Jiahui Qi
Xuanjing Wang
Tingting Fu
Ziqi Chang
Tong Zhao
Yaqin Sun
Jiayin Lu
Yi Yan
Haidong Wang
author_facet Minxing Zheng
Jiahui Qi
Xuanjing Wang
Tingting Fu
Ziqi Chang
Tong Zhao
Yaqin Sun
Jiayin Lu
Yi Yan
Haidong Wang
author_sort Minxing Zheng
collection DOAJ
description Background: In mammals, skeletal muscle typically constitutes approximately 55% of body weight. The thermogenesis of skeletal muscle increases with increased cold stress, and skeletal muscle maintains the animal’s body temperature through the heat generated by shivering. However, less attention has been paid to investigating the impact of cold stress on the fiber type makeup of skeletal muscle, especially the gastrocnemius. Consequently, this research explored how cold stress regulates muscle development and fiber type composition. Methods: A cold stress model was established by subjecting mice to a 4 °C environment for 4 hours daily. This model was combined with an in vitro siRNA-mediated knockdown model for joint validation. The impact of cold stress on skeletal muscle development and myofiber type transformation was assessed using experimental techniques, including immunofluorescence and western blotting. Results: Following cold stress, the expression level of Myosin Heavy Chain 7 (MYH7) in the mouse gastrocnemius increased, while Myosin Heavy Chain 4 (MYH4) expression decreased. Concurrently, elevated expressions of Mindbomb-1 (Mib1) and the myogenic differentiation (MyoD) were observed. Subsequent knockdown of Mib1 in C2C12 cells resulted in increased MYH4 expression and decreased MYH7 expression. Conclusion: Cold stress induces skeletal muscle fibers to shift from fast-twitch to slow-twitch through the Mib1/Notch signaling pathway.
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spelling doaj-art-66dbe90f37df499caeec908dabb4d2b42025-08-20T02:56:26ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-07-013074014110.31083/FBL40141S2768-6701(25)01780-0Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch PathwayMinxing Zheng0Jiahui Qi1Xuanjing Wang2Tingting Fu3Ziqi Chang4Tong Zhao5Yaqin Sun6Jiayin Lu7Yi Yan8Haidong Wang9College of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, Shanxi, ChinaBackground: In mammals, skeletal muscle typically constitutes approximately 55% of body weight. The thermogenesis of skeletal muscle increases with increased cold stress, and skeletal muscle maintains the animal’s body temperature through the heat generated by shivering. However, less attention has been paid to investigating the impact of cold stress on the fiber type makeup of skeletal muscle, especially the gastrocnemius. Consequently, this research explored how cold stress regulates muscle development and fiber type composition. Methods: A cold stress model was established by subjecting mice to a 4 °C environment for 4 hours daily. This model was combined with an in vitro siRNA-mediated knockdown model for joint validation. The impact of cold stress on skeletal muscle development and myofiber type transformation was assessed using experimental techniques, including immunofluorescence and western blotting. Results: Following cold stress, the expression level of Myosin Heavy Chain 7 (MYH7) in the mouse gastrocnemius increased, while Myosin Heavy Chain 4 (MYH4) expression decreased. Concurrently, elevated expressions of Mindbomb-1 (Mib1) and the myogenic differentiation (MyoD) were observed. Subsequent knockdown of Mib1 in C2C12 cells resulted in increased MYH4 expression and decreased MYH7 expression. Conclusion: Cold stress induces skeletal muscle fibers to shift from fast-twitch to slow-twitch through the Mib1/Notch signaling pathway.https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL40141cold stressmib1 genenotch signaling pathwayskeletal musclemuscle developmentmuscle fiber types
spellingShingle Minxing Zheng
Jiahui Qi
Xuanjing Wang
Tingting Fu
Ziqi Chang
Tong Zhao
Yaqin Sun
Jiayin Lu
Yi Yan
Haidong Wang
Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
Frontiers in Bioscience-Landmark
cold stress
mib1 gene
notch signaling pathway
skeletal muscle
muscle development
muscle fiber types
title Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
title_full Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
title_fullStr Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
title_full_unstemmed Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
title_short Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway
title_sort cold stress regulates muscle development and promotes muscle fiber transformation by regulating mib1 notch pathway
topic cold stress
mib1 gene
notch signaling pathway
skeletal muscle
muscle development
muscle fiber types
url https://www.imrpress.com/journal/FBL/30/7/10.31083/FBL40141
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AT jiahuiqi coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT xuanjingwang coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT tingtingfu coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT ziqichang coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT tongzhao coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
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AT jiayinlu coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT yiyan coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway
AT haidongwang coldstressregulatesmuscledevelopmentandpromotesmusclefibertransformationbyregulatingmib1notchpathway