공현준 (University of Illinois-Urbana-Champaign) | 한빛사논문 > 한빛사

한빛사논문

조회373

University of Illinois-Urbana-Champaign

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Proc. Natl. Acad. Sci. USA, May 07 2024, 121 (19) | https://doi.org/10.1073/pnas.2313590121 Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle

Kai- Yu Huang^a, Gaurav Upadhyay^b, Yujin Ahn^a,c, Masayoshoi Sakakura^d, Gelson J. Pagan-Diaz^e, Younghak Cho^f, Amanda C. Weiss^g, Chen Huang^h, Jennifer W. Mitchellⁱ, Jiahui Li^j, Yanqi Tan^h, Yu-Heng Deng^a, Austin Ellis-Mohr^d, Zhi Dou^b, Xiaotain Zhang^b, Sehong Kang^b, Qian Chen^j, Jonathan V. Sweedler^c,h, Sung Gap Im^f, Rashid Bashir^c,e, Hee Jung Chung^g, Gabriel Popescu^d, Martha U. Gillette^c,i, Mattia Gazzola^b,k, and Hyunjoon Kong^a,c,k,l,1

^aDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^bDepartment of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^cChan Zuckerberg Biohub Chicago, Chicago, IL 60642;

^dDepartment of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^eDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^fDepartment of Chemical and Biomolecular Engineering and KI for the Nano Century, Korea Advanced Institute of Science and Technology, Daejeon 305- 701, Republic of Korea;

^gDepartment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^hDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

ⁱDepartment of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^jDepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

^kCarl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; and

^lKorea University-Korea Institute of Science and Technology Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea

¹To whom correspondence may be addressed. : Hyunjoon Kong

Abstract

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-04-30)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오소재

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