Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R
Abstract
:1. Introduction
2. Results
2.1. Sequence Analysis of maIL-6 and masIL-6R
2.2. Effects of Recombinant IL-6 on the Expression of Downstream Genes in L8824 Cells
2.3. Activation of Signaling Pathways by rmaIL-6 with or without RmasIL-6R
2.4. RmaIL-6 Trans-Signaling Regulates Socs3a and Socs3b Expression via the JAK2/STAT3 Pathway in L8824 Cells and CIK Cells
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Fish
4.2. Isolation and Culture of Hepatocytes
4.3. Sequence Obtainment and Analysis
4.4. RNA Extraction and cDNA Synthesis
4.5. Expression and Purification of the Recombinant Proteins ciIL-6, maIL-6, and masIL-6R
4.6. Treatment of Cells
4.7. qPCR Analysis
4.8. Protein Extraction and Quantification
4.9. Western Blot
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
IL-6 | Interleukin-6 |
IL-6R | Interleukin-6 receptor |
IL-1β | Interleukin-1β |
Hamp | Hepcidin |
SOCS3 | Suppressor of cytokine signaling 3 |
ciIL-6 | Grass carp IL-6 |
ciIL-6R | Grass carp IL-6R |
maIL-6 | Blunt snout bream IL-6 |
maIL-6R | Blunt snout bream IL-6R |
masIL-6R | Blunt snout bream soluble IL-6R receptor |
rciIL-6 | Recombinant grass carp IL-6 protein |
rmaIL-6 | Recombinant blunt snout bream IL-6 protein |
rmasIL-6R | Recombinant blunt snout bream soluble IL-6 receptor protein |
JAK | Janus kinases |
STAT | Signal transducer and activator of transcription |
gp130 | Glycoprotein 130 |
ERK | Extracellular-signal-regulated kinase |
MEK | Mitogen-activated protein kinase |
PI3K | Phosphatidylinositol 3 kinase |
AKT | Protein kinase b |
mIL-6R | Membrane-bound IL-6R |
References
- Hirano, T.; Yasukawa, K.; Harada, H.; Taga, T.; Watanabe, Y.; Matsuda, T.; Kashiwamura, S.; Nakajima, K.; Koyama, K.; Iwamatsu, A.; et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 1986, 324, 73–76. [Google Scholar] [CrossRef] [PubMed]
- Ataie-Kachoie, P.; Pourgholami, M.H.; Richardson, D.R.; Morris, D.L. Gene of the month: Interleukin 6 (IL-6). J. Clin. Pathol. 2014, 67, 932–937. [Google Scholar] [CrossRef] [PubMed]
- Kimura, A.; Kishimoto, T. IL-6: Regulator of Treg/Th17 balance. Eur. J. Immunol. 2010, 40, 1830–1835. [Google Scholar] [CrossRef] [PubMed]
- Schmidt-Arras, D.; Rose-John, S. IL-6 pathway in the liver: From physiopathology to therapy. J. Hepatol. 2016, 64, 1403–1415. [Google Scholar] [CrossRef] [Green Version]
- Diehl, S.; Rincon, M. The two faces of IL-6 on Th1/Th2 differentiation. Mol. Immunol. 2002, 39, 531–536. [Google Scholar] [CrossRef]
- Tanaka, T.; Narazaki, M.; Kishimoto, T. Interleukin (IL-6) Immunotherapy. Cold Spring Harb. Perspect. Biol. 2018, 10, a028456. [Google Scholar] [CrossRef]
- Ridgley, L.A.; Anderson, A.E.; Maney, N.J.; Naamane, N.; Skelton, A.J.; Lawson, C.A.; Emery, P.; Isaacs, J.D.; Carmody, R.J.; Pratt, A.G. IL-6 mediated transcriptional programming of naive CD4+ T Cells in early rheumatoid arthritis drives dysregulated effector function. Front. Immunol. 2019, 10, 1535. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, T.; Narazaki, M.; Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 2014, 6, a016295. [Google Scholar] [CrossRef]
- Akira, S.; Taga, T.; Kishimoto, T. Interleukin-6 in biology and medicine. Adv. Immunol. 1993, 54, 1–78. [Google Scholar]
- Mihara, M.; Hashizume, M.; Yoshida, H.; Suzuki, M.; Shiina, M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin. Sci. 2012, 122, 143–159. [Google Scholar] [CrossRef] [Green Version]
- Theurl, I.; Schroll, A.; Sonnweber, T.; Nairz, M.; Theurl, M.; Willenbacher, W.; Eller, K.; Wolf, D.; Seifert, M.; Sun, C.C.; et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 2011, 118, 4977–4984. [Google Scholar] [CrossRef]
- Yu, H.; Pardoll, D.; Jove, R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat. Rev. Cancer 2009, 9, 798–809. [Google Scholar] [CrossRef]
- Long, M.H.; Zhang, C.; Xu, D.Q.; Fu, W.L.; Gan, X.D.; Li, F.; Wang, Q.; Xia, W.; Xu, D.G. PM2.5 aggravates diabetes via the systemically activated IL-6-mediated STAT3/SOCS3 pathway in rats’ liver. Environ. Pollut. 2020, 256, 113342. [Google Scholar] [CrossRef]
- Yoon, S.; Woo, S.U.; Kang, J.H.; Kim, K.; Kwon, M.H.; Park, S.; Shin, H.J.; Gwak, H.S.; Chwae, Y.J. STAT3 transcriptional factor activated by reactive oxygen species induces IL6 in starvation-induced autophagy of cancer cells. Autophagy 2010, 6, 1125–1138. [Google Scholar] [CrossRef] [Green Version]
- Marotta, L.L.; Almendro, V.; Marusyk, A.; Shipitsin, M.; Schemme, J.; Walker, S.R.; Bloushtain-Qimron, N.; Kim, J.J.; Choudhury, S.A.; Maruyama, R.; et al. The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24− stem cell-like breast cancer cells in human tumors. J. Clin. Investig. 2011, 121, 2723–2735. [Google Scholar] [CrossRef]
- Culig, Z. Interleukin-6 as a therapy target in oral squamous carcinoma. Expert Opin Ther. Targets 2013, 17, 53–59. [Google Scholar] [CrossRef]
- Zegeye, M.M.; Lindkvist, M.; Falker, K.; Kumawat, A.K.; Paramel, G.; Grenegard, M.; Sirsjo, A.; Ljungberg, L.U. Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells. Cell Commun. Signal 2018, 16, 55. [Google Scholar] [CrossRef]
- Rose-John, S.; Waetzig, G.H.; Scheller, J.; Grotzinger, J.; Seegert, D. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin. Ther. Targets 2007, 11, 613–624. [Google Scholar] [CrossRef]
- Baran, P.; Hansen, S.; Waetzig, G.H.; Akbarzadeh, M.; Lamertz, L.; Huber, H.J.; Ahmadian, M.R.; Moll, J.M.; Scheller, J. The balance of interleukin (IL)-6, IL-6·soluble IL-6 receptor (sIL-6R), and IL-6·sIL-6R·sgp130 complexes allows simultaneous classic and trans-signaling. J. Biol. Chem. 2018, 293, 6762–6775. [Google Scholar] [CrossRef] [Green Version]
- Wolf, J.; Rose-John, S.; Garbers, C. Interleukin-6 and its receptors: A highly regulated and dynamic system. Cytokine 2014, 70, 11–20. [Google Scholar] [CrossRef]
- Schumacher, N.; Meyer, D.; Mauermann, A.; von der Heyde, J.; Wolf, J.; Schwarz, J.; Knittler, K.; Murphy, G.; Michalek, M.; Garbers, C.; et al. Shedding of endogenous interleukin-6 receptor (IL-6R) is governed by a disintegrin and metalloproteinase (ADAM) proteases while a full-length IL-6R isoform localizes to circulating microvesicles. J. Biol. Chem. 2015, 290, 26059–26071. [Google Scholar] [CrossRef] [Green Version]
- Garbers, C.; Aparicio-Siegmund, S.; Rose-John, S. The IL-6/gp130/STAT3 signaling axis: Recent advances towards specific inhibition. Curr. Opin. Immunol. 2015, 34, 75–82. [Google Scholar] [CrossRef]
- Jones, S.A.; Rose-John, S. The role of soluble receptors in cytokine biology: The agonistic properties of the sIL-6R/IL-6 complex. Biochim. Biophys. Acta 2002, 1592, 251–263. [Google Scholar] [CrossRef] [Green Version]
- Rose-John, S. IL-6 trans-signaling via the soluble IL-6 receptor: Importance for the pro-inflammatory activities of IL-6. Int. J. Biol. Sci. 2012, 8, 1237–1247. [Google Scholar] [CrossRef]
- Schaper, F.; Rose-John, S. Interleukin-6: Biology, signaling and strategies of blockade. Cytokine Growth Factor Rev. 2015, 26, 475–487. [Google Scholar] [CrossRef]
- Redell, M.S.; Ruiz, M.J.; Alonzo, T.A.; Gerbing, R.B.; Tweardy, D.J. Stat3 signaling in acute myeloid leukemia: Ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor. Blood 2011, 117, 5701–5709. [Google Scholar] [CrossRef]
- Li, M.; Gao, J.; Li, D.; Yin, Y. CEP55 promotes cell motility via JAK2–STAT3–MMPs cascade in hepatocellular carcinoma. Cells 2018, 7, 99. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Mak, V.C.Y.; Zhou, Y.; Wang, C.; Wong, E.S.Y.; Sharma, R.; Lu, Y.; Cheung, A.N.Y.; Mills, G.B.; Cheung, L.W.T. Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer. Nat. Commun. 2019, 10, 716. [Google Scholar] [CrossRef] [Green Version]
- Ogasawara, K.; Kam, J.; Thomas, M.; Liu, L.; Liu, M.; Xue, Y.; Surapaneni, S.; Carayannopoulos, L.N.; Zhou, S.; Palmisano, M.; et al. Effects of strong and moderate CYP3A4 inducers on the pharmacokinetics of fedratinib in healthy adult participants. Cancer Chemother. Pharm. 2021, 88, 369–377. [Google Scholar] [CrossRef]
- Varela, M.; Dios, S.; Novoa, B.; Figueras, A. Characterisation, expression and ontogeny of interleukin-6 and its receptors in zebrafish (Danio rerio). Dev. Comp. Immunol. 2012, 37, 97–106. [Google Scholar] [CrossRef] [Green Version]
- Bird, S.; Zou, J.; Savan, R.; Kono, T.; Sakai, M.; Woo, J.; Secombes, C. Characterisation and expression analysis of an interleukin 6 homologue in the Japanese pufferfish, Fugu rubripes. Dev. Comp. Immunol. 2005, 29, 775–789. [Google Scholar] [CrossRef] [PubMed]
- Nam, B.H.; Byon, J.Y.; Kim, Y.O.; Park, E.M.; Cho, Y.C.; Cheong, J. Molecular cloning and characterisation of the flounder (Paralichthys olivaceus) interleukin-6 gene. Fish Shellfish Immunol. 2007, 23, 231–236. [Google Scholar] [CrossRef] [PubMed]
- Castellana, B.; Iliev, D.B.; Sepulcre, M.P.; MacKenzie, S.; Goetz, F.W.; Mulero, V.; Planas, J.V. Molecular characterization of interleukin-6 in the gilthead seabream (Sparus aurata). Mol. Immunol. 2008, 45, 3363–3370. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Q.; Li, C.; Yu, Z.X.; Zou, P.F.; Meng, Q.X.; Yao, C.L. Molecular and immune response characterizations of IL-6 in large yellow croaker (Larimichthys crocea). Fish Shellfish Immunol. 2016, 50, 263–273. [Google Scholar] [CrossRef] [Green Version]
- Iliev, D.B.; Castellana, B.; Mackenzie, S.; Planas, J.V.; Goetz, F.W. Cloning and expression analysis of an IL-6 homolog in rainbow trout (Oncorhynchus mykiss). Mol. Immunol. 2007, 44, 1803–1807. [Google Scholar] [CrossRef]
- Fu, X.; Ding, Z.; Fan, J.; Wang, H.; Zhou, F.; Cui, L.; Boxiang, C.; Wang, W.; Liu, H. Characterization, promoter analysis and expression of the interleukin-6 gene in blunt snout bream, Megalobrama amblycephala. Fish Physiol. Biochem. 2016, 42, 1527–1540. [Google Scholar] [CrossRef]
- Costa, M.M.; Maehr, T.; Diaz-Rosales, P.; Secombes, C.J.; Wang, T. Bioactivity studies of rainbow trout (Oncorhynchus mykiss) interleukin-6: Effects on macrophage growth and antimicrobial peptide gene expression. Mol. Immunol. 2011, 48, 1903–1916. [Google Scholar] [CrossRef]
- Chen, H.H.; Lin, H.T.; Foung, Y.F.; Han-You Lin, J. The bioactivity of teleost IL-6: IL-6 protein in orange-spotted grouper (Epinephelus coioides) induces Th2 cell differentiation pathway and antibody production. Dev. Comp. Immunol. 2012, 38, 285–294. [Google Scholar] [CrossRef]
- Kaneda, M.; Odaka, T.; Suetake, H.; Tahara, D.; Miyadai, T. Teleost IL-6 promotes antibody production through STAT3 signaling via IL-6R and gp130. Dev. Comp. Immunol. 2012, 38, 224–231. [Google Scholar] [CrossRef]
- Wang, X.; Guo, Y.; Wen, C.; Lv, M.; Gan, N.; Zhou, H.; Zhang, A.; Yang, K. Molecular characterization of grass carp interleukin-6 receptor and the agonistic activity of its soluble form in head kidney leucocytes. Fish Shellfish Immunol. 2019, 86, 1072–1080. [Google Scholar] [CrossRef]
- Zhou, E.; Yan, F.; Li, B.; Chen, M.; Tu, X.; Wu, S.; Wu, H.; Wei, X.; Fu, S.; Wu, L.; et al. Molecular and functional characterization of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) in Nile tilapia (Oreochromis niloticus). Dev. Comp. Immunol. 2020, 106, 103629. [Google Scholar] [CrossRef]
- Zhang, C.N.; Zhang, J.L.; Liu, W.B.; Wu, Q.J.; Gao, X.C.; Ren, H.T. Cloning, characterization and mRNA expression of interleukin-6 in blunt snout bream (Megalobrama amblycephala). Fish Shellfish Immunol. 2016, 54, 639–647. [Google Scholar] [CrossRef]
- Chang, R.; Song, L.; Xu, Y.; Wu, Y.; Dai, C.; Wang, X.; Sun, X.; Hou, Y.; Li, W.; Zhan, X.; et al. Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis. Nat. Commun. 2018, 9, 3486. [Google Scholar] [CrossRef]
- Wang, X.; Chen, J.; Zhang, R.; Liu, L.; Ma, G.; Zhu, H. Interleukin-6 in siberian sturgeon (Acipenser baeri): Molecular characterization and immune functional activity. Fish Shellfish Immunol. 2020, 102, 296–306. [Google Scholar] [CrossRef]
- Nemeth, E.; Rivera, S.; Gabayan, V.; Keller, C.; Taudorf, S.; Pedersen, B.K.; Ganz, T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Investig. 2004, 113, 1271–1276. [Google Scholar] [CrossRef] [Green Version]
- Qian, Z.M.; He, X.; Liang, T.; Wu, K.C.; Yan, Y.C.; Lu, L.N.; Yang, G.; Luo, Q.Q.; Yung, W.H.; Ke, Y. Lipopolysaccharides upregulate hepcidin in neuron via microglia and the IL-6/STAT3 signaling pathway. Mol. Neurobiol. 2014, 50, 811–820. [Google Scholar] [CrossRef]
- Wang, T.; Gao, Q.; Nie, P.; Secombes, C.J. Identification of suppressor of cytokine signalling (SOCS) 6, 7, 9 and CISH in rainbow trout Oncorhynchus mykiss and analysis of their expression in relation to other known trout SOCS. Fish Shellfish Immunol. 2010, 29, 656–667. [Google Scholar] [CrossRef]
- Modares, N.F.; Polz, R.; Haghighi, F.; Lamertz, L.; Behnke, K.; Zhuang, Y.; Kordes, C.; Haussinger, D.; Sorg, U.R.; Pfeffer, K.; et al. IL-6 trans-signaling controls liver regeneration after partial hepatectomy. Hepatology 2019, 70, 2075–2091. [Google Scholar] [CrossRef]
- Heinrich, P.C.; Behrmann, I.; Muller-Newen, G.; Schaper, F.; Graeve, L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J. 1998, 334 Pt 2, 297–314. [Google Scholar] [CrossRef] [Green Version]
- Robinson, M.B.; Deshpande, D.A.; Chou, J.; Cui, W.; Smith, S.; Langefeld, C.; Hastie, A.T.; Bleecker, E.R.; Hawkins, G.A. IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle. Am. J. Physiol. Lung Cell Mol. Physiol. 2015, 309, L129–L138. [Google Scholar] [CrossRef] [Green Version]
- Inoue-Mochita, M.; Inoue, T.; Kojima, S.; Futakuchi, A.; Fujimoto, T.; Sato-Ohira, S.; Tsutsumi, U.; Tanihara, H. Interleukin-6-mediated trans-signaling inhibits transforming growth factor-beta signaling in trabecular meshwork cells. J. Biol. Chem. 2018, 293, 10975–10984. [Google Scholar] [CrossRef] [Green Version]
- Klein, C.; Wustefeld, T.; Assmus, U.; Roskams, T.; Rose-John, S.; Muller, M.; Manns, M.P.; Ernst, M.; Trautwein, C. The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury. J. Clin. Investig. 2005, 115, 860–869. [Google Scholar] [CrossRef] [Green Version]
- Pop, V.V.; Seicean, A.; Lupan, I.; Samasca, G.; Burz, C.C. IL-6 roles—Molecular pathway and clinical implication in pancreatic cancer—A systemic review. Immunol. Lett. 2017, 181, 45–50. [Google Scholar] [CrossRef]
- Bharti, R.; Dey, G.; Mandal, M. Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: A snapshot of IL-6 mediated involvement. Cancer Lett. 2016, 375, 51–61. [Google Scholar] [CrossRef]
- Liang, F.; Ren, C.; Wang, J.; Wang, S.; Yang, L.; Han, X.; Chen, Y.; Tong, G.; Yang, G. The crosstalk between STAT3 and p53/RAS signaling controls cancer cell metastasis and cisplatin resistance via the Slug/MAPK/PI3K/AKT-mediated regulation of EMT and autophagy. Oncogenesis 2019, 8, 59. [Google Scholar] [CrossRef] [Green Version]
- Zhao, K.; Lu, Y.; Chen, Y.; Cheng, J.; Zhang, W. Dual inhibition of MAPK and JAK2/STAT3 pathways is critical for the treatment of braf mutant melanoma. Mol. Ther. Oncolytics 2020, 18, 100–108. [Google Scholar] [CrossRef]
- Duplomb, L.; Chaigne-Delalande, B.; Vusio, P.; Raher, S.; Jacques, Y.; Godard, A.; Blanchard, F. Soluble mannose 6-phosphate/insulin-like growth factor II (IGF-II) receptor inhibits interleukin-6-type cytokine-dependent proliferation by neutralization of IGF-II. Endocrinology 2003, 144, 5381–5389. [Google Scholar] [CrossRef] [Green Version]
- Ge, D.; Gao, A.C.; Zhang, Q.; Liu, S.; Xue, Y.; You, Z. LNCaP prostate cancer cells with autocrine interleukin-6 expression are resistant to IL-6-induced neuroendocrine differentiation due to increased expression of suppressors of cytokine signaling. Prostate 2012, 72, 1306–1316. [Google Scholar] [CrossRef] [Green Version]
- Kiu, H.; Nicholson, S.E. Biology and significance of the JAK/STAT signalling pathways. Growth Factors 2012, 30, 88–106. [Google Scholar] [CrossRef] [Green Version]
- Martino, N.; Ramos, R.B.; Lu, S.; Leyden, K.; Tomaszek, L.; Sadhu, S.; Fredman, G.; Jaitovich, A.; Vincent, P.A.; Adam, A.P. Endothelial SOCS3 maintains homeostasis and promotes survival in endotoxemic mice. JCI Insight 2021, 6, e147280. [Google Scholar] [CrossRef]
- Fatih, N.; Camberlein, E.; Island, M.L.; Corlu, A.; Abgueguen, E.; Detivaud, L.; Leroyer, P.; Brissot, P.; Loreal, O. Natural and synthetic STAT3 inhibitors reduce hepcidin expression in differentiated mouse hepatocytes expressing the active phosphorylated STAT3 form. J. Mol. Med. 2010, 88, 477–486. [Google Scholar] [CrossRef] [PubMed]
- Stivala, S.; Codilupi, T.; Brkic, S.; Baerenwaldt, A.; Ghosh, N.; Hao-Shen, H.; Dirnhofer, S.; Dettmer, M.S.; Simillion, C.; Kaufmann, B.A.; et al. Targeting compensatory MEK/ERK activation increases JAK inhibitor efficacy in myeloproliferative neoplasms. J. Clin. Investig. 2019, 129, 1596–1611. [Google Scholar] [CrossRef] [PubMed]
- Bai, Y.; Wang, W.; Yin, P.; Gao, J.; Na, L.; Sun, Y.; Wang, Z.; Zhang, Z.; Zhao, C. Ruxolitinib alleviates renal interstitial fibrosis in UUO mice. Int. J. Biol. Sci. 2020, 16, 194–203. [Google Scholar] [CrossRef] [PubMed]
- Song, X.; Rahimnejad, S.; Zhou, W.; Cai, L.; Lu, K. Molecular characterization of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1alpha) and its role in mitochondrial biogenesis in blunt snout bream (Megalobrama amblycephala). Front. Physiol. 2018, 9, 1957. [Google Scholar] [CrossRef]
- Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods 2001, 25, 402–408. [Google Scholar] [CrossRef]
- Ding, Z.; Zhao, X.; Cui, L.; Sun, Q.; Zhang, F.; Wang, J.; Wang, W.; Liu, H. Novel insights into the immune regulatory effects of ferritins from blunt snout bream, Megalobrama amblycephala. Fish Shellfish Immunol. 2019, 87, 679–687. [Google Scholar] [CrossRef]
- Xu, X.; Tao, L.; Wang, A.; Li, L.; Fan, K.; Shen, Y.; Li, J. Genome-wide identification of JNK and p38 gene family in Ctenopharyngodon idella and their expression profiles in response to bacterial challenge. Comp. Biochem. Physiol. Part D Genom. Proteom. 2020, 33, 100647. [Google Scholar] [CrossRef]
- Li, R.; Li, S.; Chen, Z.; Jin, Y.; Li, S.; Li, S.; Bai, Z. Grass carp (Ctenopharyngodon idella) stefin A: Systematic research on its cloning, expression, characterization and tissue distribution. Food Chem. 2021, 335, 127564. [Google Scholar] [CrossRef]
- Dai, Y.S.; Pei, W.L.; Wang, Y.Y.; Wang, Z.; Zhuo, M.Q. Topology, tissue distribution, and transcriptional level of SLC34s in response to Pi and pH in grass carp Ctenopharyngodon idella. Fish Physiol. Biochem. 2021, 47, 1383–1393. [Google Scholar] [CrossRef]
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Wang, J.; Sun, Q.; Zhang, J.; Wang, H.; Liu, H. Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R. Int. J. Mol. Sci. 2022, 23, 2019. https://doi.org/10.3390/ijms23042019
Wang J, Sun Q, Zhang J, Wang H, Liu H. Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R. International Journal of Molecular Sciences. 2022; 23(4):2019. https://doi.org/10.3390/ijms23042019
Chicago/Turabian StyleWang, Jixiu, Qianhui Sun, Jian Zhang, Huanling Wang, and Hong Liu. 2022. "Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R" International Journal of Molecular Sciences 23, no. 4: 2019. https://doi.org/10.3390/ijms23042019
APA StyleWang, J., Sun, Q., Zhang, J., Wang, H., & Liu, H. (2022). Classical Signaling and Trans-Signaling Pathways Stimulated by Megalobrama amblycephala IL-6 and IL-6R. International Journal of Molecular Sciences, 23(4), 2019. https://doi.org/10.3390/ijms23042019