Genes & Genomics

, Volume 40, Issue 11, pp 1225–1235 | Cite as

Molecular characterization and expression of suppressor of cytokine signaling (SOCS) 1, 2 and 3 under acute hypoxia and reoxygenation in pufferfish, Takifugu fasciatus

  • Dan Wang
  • Xin Wen
  • Xinyu Zhang
  • Yadong Hu
  • Xinru Li
  • Wenxu Zhu
  • Tao Wang
  • Shaowu YinEmail author
Research Article


Hypoxia seriously affects the innate immune system of fish. However, the roles of suppressor of cytokine signaling (SOCS), pivotal anti-inflammatory genes, in response to hypoxia/reoxygenation remain largely unexplored. The primary objective of this study was to elucidate the function of SOCS genes under acute hypoxia and reoxygenation in pufferfish (Takifugu fasciatus). In the present study, SOCS1, 2 and 3 were identified in T. fasciatus referred to as TfSOCS1, 2 and 3. Then, qRT-PCR and western blot analysis were employed to assess their expressions at both the mRNA and protein levels. Tissue distribution demonstrated that the three SOCS genes were predominantly distributed in gill, brain and liver. Under hypoxia challenge (1.63 ± 0.2 mg/L DO for 2, 4, 6 and 8 h), the expressions of TfSOCS1 and 3 in brain and liver at the mRNA and protein levels were significantly decreased, while their expressions showed an opposite trend in gill. Different from the expressions of TfSOCS1 and 3, the expression of TfSOCS2 was inhibited in gill, along with its increased expression in brain and liver. After normoxic recovery (7.0 ± 0.3 mg/L of DO for 4 and 12 h), most of TfSOCS genes were significantly altered at R4 (reoxygenation for 4 h) and returned to the normal level at R12 (reoxygenation for 12 h). SOCS genes played vital roles in response to hypoxia/reoxygenation challenge. Our findings greatly strengthened the relation between innate immune and hypoxia stress in T. fasciatus.


SOCS Hypoxia Reoxygenation Takifugu fasciatus 



The authors are grateful for the financial support of The National Spark Program of China (2015GA690040), The National Finance Projects of Agro-technical popularization (TG15-003), and Project Foundation of the Academic Program Development of Jiangsu Higher Education Institution (PAPD).

Supplementary material

13258_2018_719_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 KB)


  1. Bai L, Yu Z, Qian G, Qian P, Jiang J, Wang G, Bai C (2006) SOCS3 was induced by hypoxia and suppressed STAT3 phosphorylation in pulmonary arterial smooth muscle cells. Respir Physiol Neurobiol 152:83–91CrossRefPubMedGoogle Scholar
  2. Bicher HI (1974) Brain oxygen autoregulation: a protective reflex to hypoxia? Microvasc Res 8:291–313CrossRefPubMedGoogle Scholar
  3. Cheng CH, Yang FF, Liao SA, Miao YT, Ye CX, Wang AL, Tan JW, Chen XY (2015) High temperature induces apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells. J Therm Biol 53:172–179CrossRefPubMedGoogle Scholar
  4. De SAR, Penalva LO, Marcotte EM, Vogel C (2009) Global signatures of protein and mRNA expression levels. Mol Biosyst 5:1512–1526Google Scholar
  5. De SE, Di VM, Perrone GA, Mari E, Osti M, De AE, Coppola L, Tafani M, Carpi A, Russo MA (2013) Overexpression of pro-inflammatory genes and down-regulation of SOCS-1 in human PTC and in hypoxic BCPAP cells. Biomed Pharmacother 67:7–16CrossRefGoogle Scholar
  6. Duc VN, Bac NA, Hoang THT (2016) Dissolved oxygen as an indicator for eutrophication in freshwater lakes. In: International conference on environmental engineering and management for sustainable development. Hanoi, Vietnam, pp 1–6Google Scholar
  7. Ficke AD (2007) Potential impacts of global climate change on freshwater fisheries. Rev Fish Biol Fisheries 17:581–613CrossRefGoogle Scholar
  8. Gracey AY, Troll JV, Somero GN (2001) Hypoxia-induced gene expression profiling in the euryoxic fish Gillichthys mirabilis. Proc Natl Acad Sci USA 98:1993–1998CrossRefPubMedGoogle Scholar
  9. Gu Q, Kong Y, Yu ZB, Bai L, Xiao YB (2011) Hypoxia-induced SOCS3 is limiting STAT3 phosphorylation and NF-κB activation in congenital heart disease. Biochimie 93:909–920CrossRefPubMedGoogle Scholar
  10. Hammerer-Lercher A, Mair J, Bonatti J, Watzka SB, Puschendorf B, Dirnhofer S (2001) Hypoxia induces heat shock protein expression in human coronary artery bypass grafts. Cardiovasc Res 50:115–124CrossRefPubMedGoogle Scholar
  11. Hao LX, Li S (2016) Comparative analysis of the expression patterns of eight suppressors of cytokine signaling in tongue sole, Cynoglossus semilaevis. Fish Shellfish Immunol 55:595–601CrossRefPubMedGoogle Scholar
  12. Harper C, Wolf JC (2009) Morphologic effects of the stress response in fish. Ilar J 50:387–396CrossRefPubMedGoogle Scholar
  13. Itoh T, Iwahashi S, Shimoda M, Chujo D, Takita M, Sorelle JA, Naziruddin B, Levy MF, Matsumoto S (2011) High-mobility group box 1 expressions in hypoxia-induced damaged mouse islets. Transpl Proc 43:3156–3160CrossRefGoogle Scholar
  14. Jiang X, Wong AOL (2011) Grass carp SOCS and CISH: molecular cloning, functional characterization, and regulation of transcript expression by TNFα in carp hepatocytes. In: Endocrine society 93th annual meeting. Boston, USA, pp 1–2Google Scholar
  15. Jin HJ, Shao JZ, Xiang LX (2007) Identification and characterization of suppressor of cytokine signaling 3 (SOCS-3) homologues in teleost fish. Mol Immunol 44:1042–1051CrossRefPubMedGoogle Scholar
  16. Jin HJ, Shao JZ, Xiang LX, Wang H, Sun LL (2008) Global identification and comparative analysis of SOCS genes in fish: insights into the molecular evolution of SOCS family. Mol Immunol 45:1258–1268CrossRefPubMedGoogle Scholar
  17. Karim MR, Sekine M, Ukita M (2003) A model of fish preference and mortality under hypoxic water in the coastal environment. Mar Pollut Bull 47:25–29CrossRefPubMedGoogle Scholar
  18. Kato A, Doi H, Nakada T, Sakai H, Hirose S (2005) Takifugu obscurus is a euryhaline fugu species very close to Takifugu rubripes and suitable for studying osmoregulation. Bmc Physiol 5:18–28CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kim JH, Rhee JS, Lee JS, Dahms HU, Lee J, Han KN, Lee JS (2010) Effect of cadmium exposure on expression of antioxidant gene transcripts in the river pufferfish, Takifugu obscurus (Tetraodontiformes). Comp Biochem Physiol Toxicol Pharmacol CBP 152:473–479CrossRefGoogle Scholar
  20. Liu F, Zhang X, Liu Y (2000) The oxygen consumption rate and asphyxiation point in Carassius auratus Triploid. J Nat Hunan Norm Univ 23:72–75Google Scholar
  21. Liu CZ, He AY, Chen LQ, Limbu SM, Wang YW, Zhang ML, Du ZY (2016) Molecular characterization and immune response to lipopolysaccharide (LPS) of the suppressor of cytokine signaling (SOCS)-1, 2 and 3 genes in Nile tilapia (Oreochromis niloticus). Fish Shellfish Immunol 50:160–167CrossRefPubMedGoogle Scholar
  22. Maehr T, Vecino JL, Wadsworth S, Wang T, Secombes CJ (2014) Four CISH paralogues are present in rainbow trout Oncorhynchus mykiss: differential expression and modulation during immune responses and development. Mol Immunol 62:186–198CrossRefPubMedGoogle Scholar
  23. Matey V, Iftikar FI, De Boeck G, Scott GR, Sloman KA, Almeidaval VMF, Val AL, Wood CM (2011) Gill morphology and acute hypoxia: responses of mitochondria-rich, pavement, and mucous cells in the Amazonian oscar (Astronotus ocellatus) and the rainbow trout (Oncorhynchus mykiss), two species with very different approaches to the osmo-respiratory comp. Can J Zool 89:307–324CrossRefGoogle Scholar
  24. Meer DLMVD, Witte F, Bakker MAGD, Besser J, Richardson MK, Spaink HP, Leito JTD, Bagowski CP (2005) Gene expression profiling of the long-term adaptive response to hypoxia in the gills of adult zebrafish. Am J Physiol Regul Integr Comp Physiol 289:R1512–R1519CrossRefPubMedGoogle Scholar
  25. Nikinmaa M (2002) Oxygen-dependent cellular functions—why fishes and their aquatic environment are a prime choice of study. Comp Biochem Physiol Part A Mol Integr Physiol 133:1–16CrossRefGoogle Scholar
  26. Nikinmaa M, Rees BB (2005) Oxygen-dependent gene expression in fishes. Am J Physiol Regul Integr Comp Physiol 288:R1079–R1090CrossRefPubMedGoogle Scholar
  27. Qi D, Xia M, Yan C, Zhao Y, Wu R (2017) Identification, molecular evolution of toll-like receptors in a Tibetan schizothoracine fish (Gymnocypris eckloni) and their expression profiles in response to acute hypoxia. Fish Shellfish Immunol 68:102–113CrossRefPubMedGoogle Scholar
  28. Rana MK, Srivastava J, Yang M, Chen CS, Barber DL (2015) Hypoxia increases extracellular fibronectin abundance but not assembly during epithelial cell transdifferentiation. J Cell Sci 128:1083–1089CrossRefPubMedPubMedCentralGoogle Scholar
  29. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M (2008) NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453:807–811CrossRefPubMedPubMedCentralGoogle Scholar
  30. Roesner A, Mitz SA, Hankeln T, Burmester T (2008) Globins and hypoxia adaptation in the goldfish, Carassius auratus. Febs J 275:3633–3643CrossRefPubMedGoogle Scholar
  31. Ruland J (2011) Return to homeostasis: downregulation of NF-κB responses. Cambridge University Press, CambridgeGoogle Scholar
  32. Schulte PM (2014) What is environmental stress? Insights from fish living in a variable environment. J Exp Biol 217:23–34CrossRefPubMedGoogle Scholar
  33. Shepherd BS, Rees CB, Binkowski FP, Goetz FW (2012) Characterization and evaluation of sex-specific expression of suppressors of cytokine signaling (SOCS)-1 and -3 in juvenile yellow perch (Perca flavescens) treated with lipopolysaccharide. Fish Shellfish Immunol 33:468–481CrossRefPubMedGoogle Scholar
  34. Shi Y, Zhang Y, Wang C, Du C, Zhao S, Qi Z, Zhang Q, Duan H (2008) Suppressor of cytokine signaling-1 reduces high glucose-induced TGF-β1 and fibronectin synthesis in human mesangial cells. Febs Letters 582:3484–3488CrossRefPubMedGoogle Scholar
  35. Skjesol A, Liebe T, Iliev DB, Thomassen EI, Tollersrud LG, Sobhkhez M, Lindenskov JL, Secombes CJ, Jørgensen JB (2014) Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling. Dev Comp Immunol 45:177–189CrossRefPubMedGoogle Scholar
  36. Sollid J, Kjernsli A, De Angelis PM, Røhr AK, Nilsson GE (2005) Cell proliferation and gill morphology in anoxic crucian carp. AJP Regul Integr Comp Physiol 289:R1196–R1201CrossRefGoogle Scholar
  37. Strebovsky J, Walker P, Lang R, Dalpke AH (2011) Suppressor of cytokine signaling 1 (SOCS1) limits NF B signaling by decreasing p65 stability within the cell nucleus. Faseb J 25:863–874CrossRefPubMedGoogle Scholar
  38. Taylor CT, Cummins EP (2009) The Role of NF-κB in Hypoxia-Induced Gene Expression. Ann N Y Acad Sci 1177:178–184CrossRefPubMedGoogle Scholar
  39. Thanasaksiri K, Hirono I, Kondo H (2016) Identification and expression analysis of suppressors of cytokine signaling (SOCS) of Japanese flounder Paralichthys olivaceus. Fish Shellfish Immunol 58:145–152CrossRefPubMedGoogle Scholar
  40. Wang T, Secombes CJ (2008) Rainbow trout suppressor of cytokine signalling (SOCS)-1, 2 and 3: molecular identification, expression and modulation. Mol Immunol 45:1449–1457CrossRefPubMedGoogle Scholar
  41. Wang T, Gorgoglione B, Maehr T, Holland JW, Vecino JL, Wadsworth S, Secombes CJ (2011) Fish suppressors of cytokine signaling (SOCS): gene discovery, modulation of expression and function. J Signal Transduct 2011:1–20Google Scholar
  42. Wang L, Wu ZQ, Wang XL, Ren Q, Zhang GS, Liang FF, Yin SW (2016) Immune responses of two superoxide dismutases (SODs) after lipopolysaccharide or Aeromonas hydrophila challenge in pufferfish Takifugu obscurus. Aquaculture 459:1–7CrossRefGoogle Scholar
  43. Xiao J (2009) Novel mechanisms for SOCS-3 regulation in grass carp: synergistic actions of growth hormone and glucagon at the hepatic level. Dissertation. University of Hong KongGoogle Scholar
  44. Yaqoob N, Schwerte T (2010) Cardiovascular and respiratory developmental plasticity under oxygen depleted environment and in genetically hypoxic zebrafish (Danio rerio). Comp Biochem Physiol Part A Mol Integr Physiol 156:475–484CrossRefGoogle Scholar
  45. Yokogami K, Yamashita S, Takeshima H (2013) Hypoxia-induced decreases in SOCS3 increase STAT3 activation and upregulate VEGF gene expression. Brain Tumor Pathol 30:135–143CrossRefPubMedGoogle Scholar
  46. Zaninzhorov A, Tal G, Shivtiel S, Cohen M, Lapidot T, Nussbaum G, Margalit R, Cohen IR, Lider O (2005) Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and inflammation. J Immunol 175:276–285CrossRefGoogle Scholar
  47. Zhang G, Mao J, Liang F, Chen J, Zhao C, Yin S, Wang L, Tang Z, Chen S (2016) Modulated expression and enzymatic activities of Darkbarbel catfish, Pelteobagrus vachelli for oxidative stress induced by acute hypoxia and reoxygenation. Chemosphere 151:271–279CrossRefPubMedGoogle Scholar
  48. Zhang G, Zhang J, Wen X, Zhao C, Zhang H, Li X, Yin S (2017) Comparative iTRAQ-based quantitative proteomic analysis of Pelteobagrus vachelli liver against acute hypoxia: Implications in metabolic responses. Proteomics 17:1–10Google Scholar

Copyright information

© The Genetics Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.College of Life Sciences, College of Marine Sciences and EngineeringNanjing Normal UniversityNanjingChina
  2. 2.Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu ProvinceLianyungangChina

Personalised recommendations