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Affect of Socs2 loss-of-function on liver regeneration

ABSTRACT: SOCS2 Ensures Metabolic Function and Mass Restoration During Liver Regeneration - SOCS2 plays distinct and contrasting roles during liver regeneration. Early after injury, SOCS2 expression increases and limits the rate of regeneration, preserving metabolic activity. Surprisingly, at later times, the role of SOCS2 reverses to promote liver regeneration by stimulating GH release from the pituitary via effects on serum levels of insulin-like growth factor 1. Loss of SOCS2 promotes GH signaling by increasing growth hormone receptor levels and driving phosphorylation of proteins in the GH pathway, establishing a state of hyper-responsiveness to GH. These findings suggest a single protein can play contrasting roles at different times after liver injury and modulation of GH signaling achieves an optimal rate of liver regeneration to balance metabolic and restorative needs. To further understand the mechanism by which SOCS2 increases early liver regeneration, we performed microarray analysis of Socs2-null mice wildtype mice at 24 and 36 hours after hepatectomy.

ORGANISM(S): Mus musculus

PROVIDER: GSE51801 | GEO | 2014/02/01

SECONDARY ACCESSION(S): PRJNA225288

REPOSITORIES: GEO

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Project description:Although studies have established that exogenous growth hormone (GH) treatment stimulates growth in fish, its effects on target tissue gene expression are not well characterized. We assessed the effects PosilacÂ® (Monsanto Co., St. Louis, MO), a recombinant bovine somatotropin, on tissue transcript levels. Transcript abundance was measure in liver and muscle using the GRASP 16 K cDNA microarray. A selection of the genes identified as altered with the microarray, and also transcripts for insulin-like growth factors, growth hormone receptors (GHR) and myostatins were measured by realtime PCR in the liver, muscle, brain, kidney, intestine, stomach, gill and heart. In general, transcripts identified as differentially regulated in the muscle on the microarray showed similar direction of expression in the other non-hepatic tissues. Rainbow trout were selected from two high growth rate and two low growth rate families. A total of 113 and 67 transcripts were identified by microarray as differentially expressed with GH treatment across growth rate for muscle and liver respectively. The largest proportion of the transcripts represented novel transcripts, followed by immune and metabolism related genes. The immune related genes were primarily modulated in the liver and indicate activation of a non-specific immune response. The metabolic genes include lipid metabolism, oxidative phosphorylation and one carbon metabolism pathway transcripts. Most notable among the growth axis genes measured by realtime PCR were increases in GHR1 and-2 transcript in liver and muscle. Our results indicate that short-term GH treatment activates the immune system, shifts the metabolic sectors and modulates growth regulating genes. Keywords: Growth Hormone Injection Muscle and Liver Gene Expression Rainbow trout (hatched March 2005) selected for extreme growth rate were obtained from NCCCWA brood stock. Families were selected based on body weight at 7 months of age and thermal growth coefficient for the final month of growth. The two high growth families used in the study were in the top 2% in terms of growth rate, and the low growth families were in the lowest 10% for growth rate. Fish acclimated to the new tanks for two weeks prior to initiation of the treatments. Fish from each family were randomly selected to receive one of three treatments: 1) PosilacÂ® injection (120 mg/kg BW, n = 4 per family); 2) vehicle injection (n = 4 per family); or 3) untouched controls (n = 2 per family). We had determined there was no effect to growth or the GH/IGF-I axis in the vehicle treated fish, and therefore, all of the microarray hybridizations were made between the GH and vehicle injected groups. This study included a total of 16 two-channel arrays designed for the direct comparison of GH treatment levels. That is, for each of the four groups, 1) High Growth Rate Liver; 2) Low Growth Rate Liver; 3) High Growth Rate Muscle; and 4) Low Growth Rate Muscle, four slide were hybridizes using individual RNA samples from individual fish. RNA isolation from each tissue/organ sample was handled separately (without pooling) with the purpose of using biological replications. We hybridized two slides with the GH cDNA labeled with Alexa 555 and vehicle cDNA labeled with Alexa 647; and two slides, using unique RNA samples, for the with GH cDNA labeled with Alexa 647 and tissue from the vehicle injected group labeled with Alexa 647 within each tissue and growth rate. Sixteen slides were used in the current study representing 32 individual tissue samples, meaning a total of four biological replicates for each treatment group.

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Affect of Socs2 loss-of-function on liver regeneration

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