[1]
I. Janssen, S.B. Heymsfield, Z.M. Wang, R. Ross, Skeletal muscle mass
and distribution in 468 men and women aged 18-88 yr, J. Appl. Physiol.
89 (2000) 81-88. https://doi.org/10.1152/jappl.2000.89.1.81.
[2]
L.A. Rowland, N.C. Bal, M. Periasamy, The role of skeletal-muscle-based
thermogenic mechanisms in vertebrate endothermy, Biol. Rev. Camb.
Philos. Soc. 90 (2015) 1279-1297. https://doi.org/10.1111/brv.12157.
[3]
J. Jensen, P.I. Rustad, A.J. Kolnes, Y.C. Lai, The role of skeletal muscle
glycogen breakdown for regulation of insulin sensitivity by exercise,
Front. Physiol. 2 (2011) 112. https://doi.org/10.3389/fphys.2011.00112.
[4]
M. Periasamy, J.L. Herrera, F.C.G. Reis, Skeletal muscle thermogenesis
and its role in whole body energy metabolism, Diabetes Metab. J. 41
(2017) 327-336. https://doi.org/10.4093/dmj.2017.41.5.327.
[5]
J.M. Argiles, S. Busquets, B. Stemmler, F.J. Lopez-Soriano, Cancer
cachexia: understanding the molecular basis, Nat. Rev. Cancer 14 (2014)
754-762. https://doi.org/10.1038/nrc3829.
[6]
M. Muscaritoli, M. Bossola, Z. Aversa, R. Bellantone, F. Rossi Faneli,
Prevention and treatment of cancer cachexia: new insights into an old
problem.
Eur.
J.
Cancer
42
(2006)
31-41.
https://doi.org/10.1016/j.ejca.2005.07.026.
[7]
D. Sala, Z. Zorzano, Differential control of muscle mass in type 1 and
type 2 diabetes mellitus, Cell. Mol. Life Sci. 72 (2015) 3803-3817.
https://doi.org/10.1007/s00018-015-1954-7.
18
[8]
H. Miyake, I. Kanazawa, K.I. Tanaka, T. Sugimoto, Low skeletal muscle
mass is associated with the risk of all-cause mortality in patients with
type 2 diabetes mellitus, Ther. Adv. Endocrinol. Metab. 10 (2019)
2042018819842971. https://doi.org/10.1177/2042018819842971.
[9]
C. Jin, R.A. Flavell, Innate sensors of pathogen and stress: linking
inflammation to obesity, J. Allergy Clin. Immunol. 132 (2013) 387-394.
https://doi.org/10.1016/j.jaci.2013.06.022.
[10]
J. Malla, A. Zahra, S. Venugopal, T.Y. Selvamani, S.I. Shoukrie, R.
Selvaraj, R.K. Dhanoa, R.K. Hamouda, J. Mostafa, What role do
inflammatory cytokines play in cancer cachexia?, Cureus 14 (2022)
e26798. https://doi.org/10.7759/cureus.26798.
[11]
J.M.
Webster,
L.J.A.P.
Kempen,
R.S.
Hardy,
R.C.J.
Langen,
Inflammation and skeletal muscle wasting during cachexia, Front.
Physiol. 11 (2020) 597675. https://doi.org/10.3389/fphys.2020.597675.
[12]
L.
Schaefer,
Complexity
of
danger:
the
diverse
nature
of
damage-associated molecular patterns, J. Biol. Chem. 289 (2014)
35237-35245. https://doi.org/10.1074/jbc.R114.619304.
[13]
A.E. Qualls, W.M. Southern, J.A. Call, Mitochondria-cytokine crosstalk
following skeletal muscle injury and disuse: a mini-review, Am. J.
Physiol.
Cell
Phyisol.
320
(2021)
C681-C688.
https://doi.org/10.1152/ajpcell.00462.2020.
[14]
S. Lokireddy, I.W. Wijesoma, S. Bonala, M. Wei, S.K. Sze, C. McFarlane,
R. Kambadur, M. Sharma, Myostatin is a novel tumoral factor that
19
induces
cancer
cachexia,
Biochem.
J.
446
(2012)
23-36.
https://doi.org/10.1042/BJ20112024.
[15]
F. Marchildon, E. Lamarche, N. Lala-Tabbert, C. St-Louis, N.
Wiper-Bergeron, Expression of CCAAT/enhancer binding protein beta in
muscle satellite cells inhibits myogenesis in cancer cachexia, PLoS One
10 (2015) e0145583. https://doi.org/10.1371/journal.pone.0145583.
[16]
G. Zhang, Z. Liu, H. Ding, Y. Zhou, H.A. Doan, K.W.T. Sin, Z.J. Zhu, R.
Flores, Y. Wen, X. Gong, Q. Liu, Y.P. Li, Tumor induces muscle wasting in
mice through releasing extracellular Hsp70 and Hsp90, Nat. Commun. 8
(2017) 589. https://doi.org/10.1038/s41467-017-00726-x.
[17]
C. Miao, W. Zhang, L. Feng, X. Gu, Q. Shen, S. Lu, M. Fan, Y. Li, X. Guo,
Y. Ma, X. Liu, H. Wang, X. Zhang, Cancer-derived exosome miRNAs
induce skeletal muscle wasting by Bcl-2-mediated apoptosis in colon
cancer
cachexia,
Mol.
Ther.
Nucleic Acids
24
(2021) 923-938.
https://doi.org/10.1016/j.omtn.2021.04.015.
[18]
T.I. Henriksen, P.K. Davidsen, M. Pedersen, H.S. Schultz, N.S. Hansen,
T.J. Larsen, A. Vaag, B.K. Pedersen, S. Nielsen, C. Scheele,
Dysregulation of a novel miR-23b/27b-p53 axis impairs muscle stem cell
differentiation of humans with type 2 diabetes, Mol. Metab. 6 (2017)
770-779. https://doi.org/10.1016/j.molmet.2017.04.006.
[19]
T.I. Henriksen, L.V. Wigge, J. Nielsen, B.K. Pedersen, M. Sandri, C.
Scheele, Dysregulated autophagy in muscle precursor cells from humans
with
type
diabetes,
Sci.
Rep.
https://doi.org/10.1038/s41598-019-44535-2.
(2019)
8169.
20
[20]
S. Shinji, K. Umezawa, Y. Nihashi, S. Nakamura, T. Shimosato, T.
Takaya, Identification of the myogenetic oligodeoxynucleotides (myoDNs)
that promote differentiation of skeletal muscle myoblasts by targeting
nucleolin,
Front.
Cell
Dev.
Biol.
(2021)
606706.
https://doi.org/10.3389/fcell.2020.616706.
[21]
Y. Nihashi, S. Shinji, K. Umezawa, T. Ono, H. Kagami, T. Takaya,
Myogenetic oligodeoxynucleotide complexed with berberine promotes
differentiation of chicken myoblasts, Anim. Sci. J. 92 (2021) e13597.
https://doi.org/10.1002/ASJ.13597.
[22]
N. Nohira, S. Shinji, S. Nakamura, Y. Nihashi, T. Shimosato, T. Takaya,
Myogenetic oligodeoxynucleotides as anti-nucleolin aptamers inhibit the
growth of embryonal rhabdomyosarcoma cells, Biomedicines 10 (2022)
2691. https://doi.org/10.3390/biomedicines10112691.
[23]
S. Nakamura, S. Yonekura, T. Shimosato, T. Takaya, Myogenetic
oligodeoxynucleotide (myoDN) recovers the differentiation of skeletal
muscle myoblasts deteriorated by diabetes mellitus, Front. Physiol. 12
(2021) 679152. https://doi.org/10.3389/fphys.2021.679152.
[24]
Y. Nihashi, M. Yamamoto, T. Shimosato, T. Takaya, Myogenetic
oligodeoxynucleotide restores differentiation and reverses inflammation
of myoblasts aggravated by cancer-conditioned medium, Muscles 1 (2022)
111-120. https://doi.org/10.3390/muscles1020012.
[25]
E.K. Enwere, E.C. Lacasse, N.J. Adam, R.G. Korneluk, Role of the
TWEAK-Fn14-cIAP1-NF-κB
signaling
axis
in
the
regulation
of
21
myogenesis and muscle homeostasis, Front. Immunol. 5 (2014) 34.
https://doi.org/10.3389/fimmu.2014.00034.
[26]
L.H. Mariero, M.K. Torp, C.M. Heiestad, A. Baysa, Y. Li, G. Valen, J.
Vaage, K.O. Stenslokken, Inhibiting nucleolin reduces inflammation
induced by mitochondrial DNA in cardiomyocytes exposed to hypoxia and
reoxygenation,
Br.
J.
Pharmacol.
176
(2019)
4360-4372.
https://doi.org/10.1111/bph.14830.
[27]
Y. Nihashi, M. Miyoshi, K. Umezawa, T. Shimosato, T. Takaya,
Identification of a novel osteogenetic oligodeoxynucleotide (osteoDN) that
promotes osteoblast differentiation in a TLR9-independent manner,
Nanomaterials 12 (2022) 1680. https://doi.org/10.3390/nano12101680.
[28]
L. Fang, P.F. Zhang, K.K. Wang, Z.L. Xiao, M. Yang, Z.X. Yu, Nucleolin
promotes Ang II‑induced phenotypic transformation of vascular smooth
muscle cells via interaction with tropoelastin mRNA, Int. J. Mol. Med. 43
(2019) 1597-1610. https://doi.org/10.3892/ijmm.2019.4090.
[29]
L. Fang, K.K. Wang, P.F. Zhang, T. Li, Z.L. Xiao, M. Yang, Z.X. Yu,
Nucleolin promotes Ang II-induced phenotypic transformation of
vascular smooth muscle cells by regulating EGF and PDGF-BB, J. Cell.
Mol. Metab. 24 (2020) 1917-1933. https://doi.org/10.1111/jcmm.14888.
[30]
T. Mitani, T. Takaya, N. Harada, S. Katayama, R. Yamaji, S. Nakamura,
H. Ashida, Theophylline suppresses interleukin-6 expression by
inhibiting glucocorticoid receptor signaling in pre-adipocytes, Arch.
Biochem.
Biophys.
646
https://doi.org/10.1016/j.abb.2018.04.001.
(2018)
98-106.
22
[31]
K.J. Veazey, M.C. Golding, Selection of stable reference genes for
quantitative
rt-PCR
extra-embryonic
stem
comparisons
cells,
of
PLoS
mouse
One
embryonic
(2011)
and
e27592.
https://doi.org/10.1371/journal.pone.0027592.
[32]
K.E. Beazley, S. Deasey, F. Lima, M.V. Nurminskaya, Transglutaminase
2-mediated activation of beta-catenin signaling has a critical role in
warfarin-induced vascular calcification, Arterioscler. Thromb. Vasc. Biol.
32 (2012) 123-130. https://doi.org/10.1161/ATVBAHA.111.237834.
[33]
M. Sugimoto, H. Arai, Y. Tamura, T. Murayama, P. Khaengkhan, T.
Nishio, K. Ono, H. Ariyasu, T. Akamizu, Y. Ueda, T. Kita, S. Harada, K.
Kamei, M. Yokode, Mulberry leaf ameliorates the expression profile of
adipocytokines by inhibiting oxidative stress in white adipose tissue in
db/db
mice,
Atherosclerosis
204
(2009)
388-394.
https://doi.org/10.1016/j.atherosclerosis.2008.10.021.
[34]
U.A. Kohler, F. Bohm, F. Rolfs, M. Egger, T. Hornemann, M. Pasparakis,
A. Weber, S. Werner, NF-κB/RelA and Nrf2 cooperate to maintain
hepatocyte integrity and to prevent development of hepatocellular
adenoma,
J.
Hepatol.
64
(2016)
94-102.
https://doi.org/10.1016/j.jhep.2015.08.033.
[35]
R. Takanabe, K. Ono, Y. Abe, T. Takaya, T. Horie, H. Wada, T. Kita, N.
Satoh,
A. Shimatsu,
K.
Hasegawa, Up-regulated expression of
microRNA-143 in association with obesity in adipose tissue of mice fed
high-fat diet, Biochem. Biophys. Res. Commun. 376 (2008) 728-732.
https://doi.org/10.1016/j.bbrc.2008.09.050.
23
[36]
A. Soultanova, Z. Mikulski, U. Pfeil, V. Grau, W. Kummer, Calcitonin
peptide family members are differentially regulated by LPS and inhibit
functions of rat alveolar NR8383 macrophages, PLoS One 11 (2016)
e0163483. https://doi.org/10.1371/journal.pone.0163483.
[37]
X. Shan, Y. Zhang, H. Chen, L. Dong, B. Wu, T. Xu, J. Hu, Z. Liu, W.
Wang, L. Wu, Z. Feng, G. Liang, Inhibition of epidermal growth factor
receptor attenuates LPS-induced inflammation and acute lung injury in
rats,
Oncotarget
(2017)
26648-26661.
https://doi.org/10.18632/oncotarget.15790.
[38]
A. Sarrion-Perdigones, Y. Gonzalez, K.J.T. Venken, Rapid and efficient
synthetic assembly of multiplex luciferase reporter plasmids for the
simultaneous monitoring of up to six cellular signaling pathways, Curr.
Protoc. Mol. Biol. 131 (2020) e121. https://doi.org/10.1002/cpmb.121.
[39]
E. Tanaka, T. Mitani, M. Nakashima, E. Yonemoto, H. Fujii, H. Ashida,
Theobromine enhances the conversion of white adipocytes into beige
adipocytes in a PPARγ activation-dependent manner, J. Nutr. Biochem.
100 (2022) 108898. https://doi.org/10.1016/j.jnutbio.2021.108898.
[40]
Y. Nihashi, T. Ono, H. Kagami, T. Takaya, Toll-like receptor
ligand-dependent inflammatory responses in chick skeletal muscle
myoblasts,
Dev.
Comp.
Immunol.
91
(2019)
115-122.
https://doi.org/10.1016/j.dci.2018.10.013.
[41]
T. Liu, L. Zhang, D. Joo, S.C. Sun, NF-κB signaling in inflammation,
Signal
Transduct.
Target.
Ther.
https://doi.org/10.1038/sigtrans.2017.23.
(2017)
e17023.
24
[42]
C. Zuo, X. Zhao, Y. Shi, W. Wu, N. Zhang, J. Xu, C. Wang, G. Hu, X.
Zhang, TNF-α inhibits SATB2 expression and osteoblast differentiation
through NF-κB and MAPK pathways, Oncotarget 9 (2018) 4833-4850.
https://doi.org/10.18632/oncotarget.23373.
[43]
B. Ma, M.O. Hottiger, Crosstalk between Wnt/β-catenin and NF-κB
signaling pathway during inflammation, Front. Immunol. 7 (2016) 378.
https://doi.org/10.3389/fimmu.2016.00378.
[44]
S.D.
Gopinath,
S.
Narumiya,
J.
Dhawan,
The
RhoA effector
mDiaphanous regulates MyoD expression and cell cycle progression via
SRF-dependent and SRF-independent pathways, J. Cell Sci. 120 (2007)
3086-3098. https://doi.org/10.1242/jcs.006619.
[45]
J. Li, Y. Wang, Y. Wang, Y. Yan, H. Tong, S. Li, Fibronectin type III
domain containing four promotes differentiation of C2C12 through the
Wnt/β-catenin signaling pathway, FASEB J. 34 (2020) 7759-7772.
https://doi.org/10.1096/fj.201902860RRR.
[46]
W. Jia, Z. Yao, J. Zhao, Q. Guan, L. Gao, New perspectives of
physiological and pathological functions of nucleolin (NCL), Life Sci. 186
(2017) 1-10. https://doi.org/10.1016/j.lfs.2017.07.025.
[47]
P. Csermely, T. Schnaider, B. Cheatham, M.O.J. Olson, C.R. Kahn,
Insulin induces the phosphorylation of nucleolin, J. Biol. Chem. 268
(1993) 9747-9752. https://doi.org/10.1016/s0021-9258(18)98411-5.
[48]
M. Terrasi, E. Fiorio, A. Mercanti, M. Koda, C.A. Moncada, S. Sulkowski,
S. Merali, A. Russo, E. Surmacz, Functional analysis of the -2548G/A
25
leptin gene polymorphism in breast cancer cells, Int. J. Cancer 125
(2009) 1038-1044. https://doi.org/10.1002/ijc.24372.
[49]
J.A. McCubrey, L.S. Steelman, F.E. Bertrand, N.M. Davis, S.L. Abrams,
G. Montalto, A.B. D’Assoro, M. Libra, F. Nicoletti, R. Maestro, J. Basecke,
L. Cocco, M. Cervello, A.M. Martelli, Multifaceted roles of GSK-3 and
Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for
therapeutic
intervention,
Leukemia
28
(2014)
15-33.
https://doi.org/10.1038/leu.2013.184.
[50]
S. Reister, C. Mahotka, N. van den Hofel, E. Crinstein, Nucleolin
promotes Wnt signaling in human hematopoietic stem/progenitor cells,
Leukemia
33
(2019)
1052-1054.
https://doi.org/10.1038/s41375-019-0401-4.
[51]
L. Fang, K.K. Wang, Q. Huang, F. Cheng, F. Huang, W.W. Liu, Nucleolin
mediates LPS-induced expression of inflammatory mediators and
activation of signaling pathways, Curr. Med. Sci. 40 (2020) 646-653.
https://doi.org/10.1007/s11596-020-2229-6.
[52]
M. Yamamoto, M. Miyoshi, K. Morioka, T. Mitani, T. Takaya, An
anti-nucleolin aptamer, iSN04, inhibits inflammatory responses in
myoblasts by modulating β-catenin/NF-κB signaling pathway, bioRxiv
(2023) 535227. https://doi.org/10.1101/2023.04.01.535227.
26
Figure legends
Fig. 1. iSN04 inhibits NF-κB-dependent inflammatory gene expression in
myoblast cell line C2C12. (A) qPCR results of TNF-α (Tnf), IL-6 (Il6), and
NF-κB p65 subunit (Rela) expression in the C2C12 cells pre-treated with 10
μM iSN04 for 3 h and then treated with 50 ng/ml TNF-α, 100 ng/ml
Pam3CSK4, or 100 ng/ml FSL-1 for 2 h. * p < 0.05, ** p < 0.01 vs control; † p <
0.05,
††
p < 0.05 vs ligand. n = 3-4. (B) Relative NF-κB-Luc activities in the
C2C12 cells pre-treated with 10 μM iSN04 for 3 h and then treated with 50
ng/ml TNF-α or 100 ng/ml Pam3CSK4 for 40 h. ** p < 0.01 vs control;
p<
0.05, †† p < 0.05 vs ligand. n = 3.
Fig. 2. iSN04 inhibits nuclear translocation of NF-κB. (A and B)
Representative images of NF-κB staining of the C2C12 cells pre-treated with
10 μM iSN04 for 3 h and then treated with 50 ng/ml TNF-α (A) or 100 ng/ml
Pam3CSK4 (B) for 30 min. Scale bar, 50 μm.
Fig. 3. iSN04 inhibits GSK-3β phosphorylation and β-catenin activation. (A)
Representative images of β-catenin staining of the C2C12 cells pre-treated
with 10 μM iSN04 for 3 h and then treated with 50 ng/ml TNF-α for 1 h.
Scale bar, 50 μm. (B) Representative images and quantification of Western
blotting of β-catenin and GAPDH from C2C12 cells treated as in panel A. **
p < 0.01 vs control, † p < 0.05 vs TNF-α. n = 3.
27
Fig. 4. iSN04 inhibits NF-κB-dependent inflammatory gene expression in
smooth muscle cell line A10 and adipocyte-like cell line 3T3-L1. (A) qPCR
results of IL-6 (Il6), IL-8 (Cxcl8), and MCP-1 (Ccl2) expression in A10 cells
pre-treated with 10 μM iSN04 for 3 h and subsequently treated with 50
ng/ml TNF-α for 4 h. * p < 0.05, ** p < 0.01 vs control; † p < 0.05, †† p < 0.05 vs
TNF-α. n = 3. (B) Relative NF-κB-Luc activities in the A10 cells pre-treated
with 10 μM iSN04 for 3 h and subsequently treated with 3 ng/ml TNF-α for
40 h. ** p < 0.01 vs control,
p < 0.05 vs TNF-α. n = 3. (C) qPCR results of
TNF-α (Tnf) and IL-6 (Il6) expression in the 3T3-L1 cells pre-treated with 30
μM iSN04 for 3 h and subsequently treated with 5 ng/ml TNF-α or 10 ng/ml
Pam3CSK4 for 2 h. * p < 0.05, ** p < 0.01 vs control; † p < 0.05,
ligand. n = 3-4.
††
p < 0.05 vs
Figure 1
1.5
††
1.0
0.5
0.0
iSN04
iSN04
iSN04
TNF
TNF
Pam
Pam
FSL
FSL
**
**
30
††
Il6 / Ywhaz
Il6 / Ywhaz
20
††
10
50
40
30
20
10
**
††
iSN04
iSN04
iSN04
TNF
TNF
Pam
Pam
FSL
FSL
iSN04
FSL
FSL
2.0
Rela / Ywhaz
Rela / Ywhaz
††
1.5
1.0
0.5
0.0
2.0
1.5
1.0
0.5
0.0
iSN04
TNF
TNF
iSN04
Pam Pam
Pam3CSK4 (100 ng/ml)
NF-κB-Luc
**
25
20
15
10
2.0
1.5
1.0
0.5
0.0
TNF-α (50 ng/ml)
NF-κB-Luc
**
**
10
Tnf / Ywhaz
FSL-1 (100 ng/ml)
Il6 / Ywhaz
Tnf / Ywhaz
2.0
Pam3CSK4 (100 ng/ml)
Tnf / Ywhaz
TNF-α (50 ng/ml)
Rela / Ywhaz
50
40
30
20
10
**
††
iSN04
iSN04
TNF
TNF
Pam
Pam
Figure 2
Control
TNF-α
iSN04 + TNF-α
Control
Pam3CSK4
iSN04 + Pam3CSK4
DAPI
NF-κB
DAPI
NF-κB
Figure 3
TNF-α
iSN04 + TNF-α
DAPI
β-catenin
Control
β-catenin / GAPDH
β-catenin
iSN04
TNF-α
GAPDH
**
††
iSN04
TNF
TNF
Figure 4
TNF-α (50 ng/ml)
1.0
0.5
0.0
10
**
30
††
20
10
iSN04
iSN04
iSN04
TNF
TNF
TNF
TNF
TNF
TNF
TNF-α (5 ng/ml)
**
Tnf / Ywhaz
**
Pam3CSK4 (10 ng/ml)
iSN04
iSN04
iSN04
TNF
TNF
TNF
TNF
Pam
Pam
**
††
Il6 / Ywhaz
NF-κB-Luc
††
TNF-α (3 ng/ml)
40
**
15
Tnf / Ywhaz
20
Ccl2 / Rpl19
Cxcl8 / Rpl19
1.5
Il6 / Ywhaz
Il6 / Rpl19
2.0
**
50
40
30
20
10
††
iSN04
iSN04
TNF
TNF
Pam
Pam
...