SHORT COMMUNICATION IGF-1 induces SOCS-2 but not SOCS-1 and SOCS-3 transcription in juvenile Nile tilapia (Oreochromis niloticus) Cai-Zhi Liu 1 , Yuan Luo 1 , Samwel Mchele Limbu 1,2 , Li-Qiao Chen 1, * and Zhen-Yu Du 1, * ABSTRACT Insulin-like growth factor-1 (IGF-1) plays a crucial role in regulating growth in vertebrates whereas suppressors of cytokine signaling (SOCS) act as feedback inhibitors of the GH/IGF-1 axis. Although SOCS-2 binds the IGF-1 receptor and inhibits IGF-1-induced STAT3 activation, presently there is no clear evidence as to whether IGF-1 could induce SOCS gene expression. The current study aimed to determine whether IGF-1 could induce the transcription of SOCS in juvenile Nile tilapia (Oreochromis niloticus). We show that there is a common positive relationship between the mRNA expression of IGF-I and SOCS-2 under different nutritional statuses and stimulants, but not the mRNA expression of SOCS-1 and SOCS-3. Furthermore, rhIGF-1 treatment and transcriptional activity assay confirmed the hypothesis that IGF-1 could induce SOCS-2 expression, whereas it had no effect or even decreased the expression of SOCS-1 and SOCS-3. Overall, we obtained evidence that the transcription of SOCS-2, but not SOCS-1 or SOCS-3, could be induced by IGF signaling, suggesting that SOCS-2 serves as a feedback suppressor of the IGF-1 axis in juvenile Nile tilapia. KEY WORDS: Nile tilapia, Insulin-like growth factor, Suppressor of cytokine signaling, Modulation INTRODUCTION Insulin-like growth factor-1 (IGF-1) has extensive functions in differentiation, development, reproduction, growth and aging in vertebrates (Adashi, 1998; Cohen et al., 2009; Gougeon, 1996; Laron, 2001; Rommel et al., 2001). IGF-1 is primarily transcribed, synthesized and secreted in the liver (Daughaday and Rotwein, 1989; Yakar et al., 1999). Generally, the synthesis of IGF-1 is induced by growth hormone (GH) through the JAK2/STAT5 pathway (Teglund et al., 1998). However, GH is not the only regulator of IGF-1 and its activation can occur independent of GH during early development (Nakae et al., 2001). The suppressor of cytokine signaling (SOCS) family of proteins was originally described as one of the most important feedback inhibitors of JAK/STAT signaling (Croker et al., 2008). SOCS-1 and SOCS-3, via inhibition of JAK/STAT signaling and competition for the binding of IRS1, cause induced insulin resistance in obesity and diabetes models (Howard and Flier, 2006; Yoshimura et al., 2007). GH treatment induces SOCS-2 and SOCS-3 expression in the liver, both in vivo and in vitro (Adams et al., 1998; Tollet-Egnell et al., 1999). Moreover, SOCS-2 is proposed to be a feedback inhibitor of the GH/IGF-1 axis, which is reflected by the overgrowth phenotype of SOCS-2-deficient mice (Metcalf et al., 2000). Although SOCS-2 binds the IGF-1 receptor and inhibits IGF-1-induced STAT3 activation (Dey et al., 1998; Zong et al., 2000), presently there is no clear evidence as to whether IGF-1 could induce SOCS gene expression. In teleost fishes, IGF-1 is an important regulator of somatic growth and is deemed as a potential endocrine biomarker that can both reflect and predict growth rates in fish (Picha et al., 2008). Recently, a comprehensive study indicated that type II SOCS could be induced by GH and inhibit GH-induced IGF-1 expression in carp hepatocytes, suggesting that SOCS presumably has a feedback regulation role in GH signaling in fish (Jiang et al., 2016). However, knowledge about the feedback regulation of the IGF-1 signaling system is still limited. Our previous study suggested that juvenile Nile tilapia SOCS-1 and SOCS-3 are mainly involved in innate immune response regulation, whereas SOCS-2 functions are primarily in metabolic regulation (Liu et al., 2016). In the present study, we assessed the simultaneous expression of IGF-1 and SOCS-1, -2 and -3 under treatments with different nutritional statuses and stimulants. Furthermore, we tested the hypothesis that IGF-1 could induce SOCS-2 expression in juvenile Nile tilapia. This hypothesis was confirmed using rhIGF-1 treatment and a transcriptional activity assay. Our results demonstrate a common positive relationship between the mRNA expression of IGF-I and SOCS-2 under different treatments. Furthermore, IGF-1 can induce SOCS-2 expression, whereas it has no effect or even decreases the expression of SOCS-1 and SOCS-3 in juvenile Nile tilapia. MATERIALS AND METHODS This research project was approved by the Animal Ethics Committee of East China Normal University and all experiments were conducted according to the principles and procedures of the Laboratory Animal Management Ordinance of China. Experimental animals Juvenile male Nile tilapia (approximately 2.0 g) were obtained from a commercial farm in Qingyuan (Guangdong Province, China) and acclimated in 300-liter opaque polyethylene tanks. Fish were fed with a commercial diet (Tongwei, Chengdu, Sichuan province, China) prior to experiments. Water temperature was maintained at 28±2°C with a 12 h:12 h light:dark photoperiod, and one-third by volume of the water was changed every day. Experimental design and sampling After 1 week of acclimation, the fish were divided into two sets of experiments. In one set, 80 visually healthy juvenile Nile tilapia with relatively similar masses (3.0±0.5 g) were randomly distributed into four 140-liter opaque polyethylene tanks (20 fish each tank) in order to study the simultaneous expression of IGF-1 Received 14 February 2018; Accepted 8 April 2018 1 Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai 200241, People’s Republic of China. 2 Department of Aquatic Sciences and Fisheries Technology, P. O. Box 35064, University of Dar es Salaam, Dar es Salaam, Tanzania. *Authors for correspondence (zydu@bio.ecnu.edu.cn; lqchen@bio.ecnu.edu.cn) Z.-Y.D., 0000-0001-6581-5313 1 © 2018. Published by The Company of Biologists Ltd | Journal of Experimental Biology (2018) 221, jeb179291. doi:10.1242/jeb.179291 Journal of Experimental Biology