CaMKⅣ信号通过调控肌纤维功能及肌内炎症影响肌损伤修复

王涵, 厉洋洋, 菅晓婷, 黄静雯, 蓝海强, 王琪森, 段文彪, 廖华

中国临床解剖学杂志 ›› 2026, Vol. 44 ›› Issue (5) : 543-549.

PDF(8529 KB)
PDF(8529 KB)
中国临床解剖学杂志 ›› 2026, Vol. 44 ›› Issue (5) : 543-549. DOI: 10.13418/j.issn.1001-165x.2026.5.07
实验研究

CaMKⅣ信号通过调控肌纤维功能及肌内炎症影响肌损伤修复

  • 王涵1,    厉洋洋2,    菅晓婷2,    黄静雯2,    蓝海强2,    王琪森2,    段文彪2*,    廖华2*
作者信息 +

CaMKⅣ signaling affects muscle injury repair by regulating muscle fiber function and intramuscular inflammation

  • Wang Han1, Li Yangyang 2, Jian Xiaoting2, Huang Jingwen2, Lan Haiqiang2, Wang Qisen2, Duan Wenbiao2*, Liao Hua2*
Author information +
文章历史 +

摘要

目的    探究CaMKⅣ信号对肌纤维功能及肌内炎症的影响。  方法    选择野生C57BL/6 鼠(对照)、CaMKⅣ敲除鼠(CaMKⅣ-/-)。Cardiotoxin(CTX)胫骨前肌(TA)注射诱导小鼠急性肌损伤。比较两组动物损伤肌内肌纤维的修复速度、肌内炎症细胞浸润。体外分化培养原代WT,或CaMKⅣ-/- 成肌细胞(MPCs),与巨噬细胞共培养,对比分析巨噬细胞功能差异。  结果    与WT鼠相比,CaMKⅣ-/-鼠损伤肌肌再生延迟、炎性浸润显著,以M1巨噬细胞为主,M2细胞数量、增殖比例显著下调。体外炎性环境中,CaMKⅣ-/--MPCs共培养体系中的M2巨噬细胞数量与增殖比例较之WT- MPCs均显著下调(P<0.05)。  结论    内源CaMKⅣ信号活化肌纤维参与调控巨噬细胞表型,可促进损伤肌内M2型巨噬细胞增殖分化,有助于炎症撤退,加快肌修复。

Abstract

Objective    To investigate the effects of CaMKⅣ signaling on muscle fiber function and intramuscular inflammation.   Methods   Wild C57BL/6 mice (control group) and CaMKⅣ knockout mice (CaMKⅣ-/-) were selected. Cardiotoxin (CTX) was injected into the anterior tibial muscle to induce acute muscle injury in mice. The repair speed of injured muscle fibers and the infiltration of inflammatory cells in the muscle were compared between the two groups of animals. Primary WT or CaMKⅣ-/- myogenic progenitor cells (MPCs) were differentiated and cultured in vitro, and co-cultured with macrophages. The functional differences of macrophages were compared.   Results   Compared with WT mice, CaMKⅣ-/- mice had delayed muscle fiber regeneration and significant inflammatory infiltration, mainly dominated by M1 macrophages, with significantly decreased M2 cell numbers and proliferation ratios. In the inflammatory environment in vitro, the number and proliferation ratio of M2 macrophages in the CaMKⅣ-/-- MPCs co-culture system were significantly lower than those in the WT-MPCs (P<0.05).   Conclusions    The endogenous CaMKⅣ signaling activates muscle fibers to participate in regulating the phenotype of macrophages, promoting the proliferation and differentiation of M2-type macrophages in the injured muscle, facilitating inflammation resolution and accelerating muscle repair.

关键词

CaMKⅣ /   /   / 巨噬细胞胞 /   /   / 炎症 /   /   / 肌纤维

Key words

CaMKⅣ /   /   / Macrophages /   /   / Inflammation /   /   / Muscle fibers

引用本文

导出引用
王涵, 厉洋洋, 菅晓婷, 黄静雯, 蓝海强, 王琪森, 段文彪, 廖华. CaMKⅣ信号通过调控肌纤维功能及肌内炎症影响肌损伤修复[J]. 中国临床解剖学杂志. 2026, 44(5): 543-549 https://doi.org/10.13418/j.issn.1001-165x.2026.5.07
Wang Han, Li Yangyang, Jian Xiaoting, Huang Jingwen, Lan Haiqiang, Wang Qisen, Duan Wenbiao, Liao Hua. CaMKⅣ signaling affects muscle injury repair by regulating muscle fiber function and intramuscular inflammation[J]. Chinese Journal of Clinical Anatomy. 2026, 44(5): 543-549 https://doi.org/10.13418/j.issn.1001-165x.2026.5.07
中图分类号: R392.31   

参考文献

[1] Wang SL, Ribar TJ, Means AR. Expression of Ca(2+)/calmodulin-dependent protein kinase IV (caMKIV) messenger RNA during murine embryogenesis[J]. Cell Growth  Differ, 2001, 12(7): 351-361.
[2] Racioppi L, Means AR. Calcium/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveller[J]. Trends Immunol, 2008, 29(12): 600-607. DOI:10.1016/j.it.2008.08.005.
[3]  Naz H, Islam A, Ahmad F, et al. Calcium/calmodulin-dependent protein kinase IV: A multifunctional enzyme and potential therapeutic target[J]. Prog Biophys Mol Biol, 2016, 121(1): 54-65. DOI:10.1016/j.pbiomolbio.2015.12.016.
[4]  Koga T, Kawakami A. The role of CaMK4 in immune responses[J]. Mod Rheumatol, 2018,28(2):211-214. DOI:10.1080/14397595.2017. 1413964.
[5] Chin ER. The role of calcium and calcium/calmodulin-dependent kinases in skeletal muscle plasticity and mitochondrial biogenesis[J]. Proc Nutr Soc, 2004, 63(2): 279-286. DOI:10.1079/PNS2004335.
[6] Chin ER. Role of Ca2+/calmodulin-dependent kinases in skeletal muscle plasticity[J]. J Appl Physiol (1985), 2005, 99(2): 414-423. DOI:10.1152/japplphysiol.00015.2005.
[7] Shi D, Gu R, Song Y, et al. Calcium/Calmodulin-Dependent Protein Kinase IV (CaMKIV) Mediates Acute Skeletal Muscle Inflammatory Response[J]. Inflammation, 2018, 41(1):199-212. DOI:10.1007/s10753- 017-0678-2.
[8]  Marino M, Scuderi F, Provenzano C, et al. Skeletal muscle cells: from local inflammatory response to active immunity[J]. Gene Ther, 2011, 18(2): 109-116. DOI:10.1038/gt.2010.124.
[9] Duchesne E, Dufresne SS, Dumont NA. Impact of Inflammation and Anti-inflammatory Modalities on Skeletal Muscle Healing: From Fundamental Research to the Clinic[J]. Phys Ther, 2017, 97(8): 807-817. DOI:10.1093/ptj/pzx056.
[10]Al-Shanti N, Stewart CE. Ca2+/calmodulin-dependent transcriptional pathways: potential mediators of skeletal muscle growth and development[J]. Biol Rev Camb Philos Soc, 2009, 84(4): 637-652. DOI:10.1111/j.1469-185X.2009.00090.x.
[11]Wang SL, Ribar TJ, Means AR. Expression of Ca(2+)/calmodulin-dependent protein kinase IV (caMKIV) messenger RNA during murine embryogenesis[J]. Cell Growth  Differ, 2001, 12(7): 351-361.
[12]Wu H, Kanatous SB, Thurmond FA, et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK[J]. Science, 2002, 296(5566): 349-352. DOI:10.1126/science.1071163.
[13]Guerfali I, Manissolle C, Durieux A, et al. Calcineurin A and CaMKIV transactivate PGC-1alpha promoter, but differentially regulate cytochrome c promoter in rat skeletal muscle[J]. Pflugers Arch, 2007, 454(2): 297-305. DOI:10.1007/s00424-007-0206-6.
[14]Pang J, Koh TJ. Proliferation of monocytes and macrophages in homeostasis, infection, injury, and disease[J]. J Leukoc Biol, 2023, 114(6): 532-546. DOI:10.1093/jleuko/qiad093.
[15]Forcina L, Cosentino M, Musarò A. Mechanisms Regulating Muscle Regeneration: Insights into the Interrelated and Time-Dependent Phases of Tissue Healing[J]. Cells, 2020, 9(5): 1297. DOI:10.3390/cells9051 297.
[16]Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice[J]. Science, 1999, 285(5425): 248-251. DOI:10.1126/science.285.5425.248.
[17]Koga T, Hedrich CM, Mizui M, et al. CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance[J]. J Clin Invest, 2014, 124(5): 2234-2245. DOI:10.1172/JCI73411.

基金

广东省自然科学基金(2025A1515011221)

PDF(8529 KB)

Accesses

Citation

Detail

段落导航
相关文章

/

〈 〉