Growth Hormone Receptor Gene is Essential for Chicken Mitochondrial Function In Vivo and In Vitro

Hu, Bowen; Hu, Shuang; Yang, Ming; Liao, Zhiying; Zhang, Dexiang; Luo, Qianyi; Zhang, Xiquan; Li, Hongmei

doi:10.3390/ijms20071608

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…GHR ablation is detrimental to osteocyte and fibroblast mitochondrial function ( Liu et al, 2019 ). Consistently, mitochondrial function is impeded in the skeletal muscle of SLD chickens and GHR knockdown cells, indicating that GHR promotes mitochondrial function in vivo and in vitro ( Hu et al, 2019 ). However, these data are in conflict with a previous report that demonstrated an enhanced mitochondrial function in the liver, muscle, heart, kidneys, and brain of aged GHRKO mice ( Brown-Borg et al, 2009 ).…”

Section: The Effects Of Gh–ghr–igf1 Axis On Mitochondrial Functionmentioning

confidence: 91%

“…However, several recent findings are different from the previous results. Our previous study has revealed that the gene expression of mitochondrial biogenesis markers ( PGC1 α, NRF1 , and TFAM ) and mtDNA-encoded OXPHOS genes are all downregulated in the skeletal muscle of SLD chickens and GHR knockdown cells ( Hu et al, 2019 ). At the same time, we observed that the enzymatic activities of OXPHOS complexes (complexes I, II, III, and IV) are reduced in the skeletal muscle of SLD chickens and GHR knockdown cells, indicating that GHR exhibits a positive effect on mitochondrial biogenesis.…”

Section: The Effects Of Growth Hormone Receptor On Mitochondrial Biogmentioning

confidence: 99%

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A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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Mitochondrial function is multifaceted in response to cellular energy homeostasis and metabolism, with the generation of adenosine triphosphate (ATP) through the oxidative phosphorylation (OXPHOS) being one of their main functions. Selective elimination of mitochondria by mitophagy, in conjunction with mitochondrial biogenesis, regulates mitochondrial function that is required to meet metabolic demand or stress response. Growth hormone (GH) binds to the GH receptor (GHR) and induces the JAK2/STAT5 pathway to activate the synthesis of insulin-like growth factor 1 (IGF1). The GH–GHR–IGF1 axis has been recognized to play significant roles in somatic growth, including cell proliferation, differentiation, division, and survival. In this review, we describe recent discoveries providing evidence for the contribution of the GH–GHR–IGF1 axis on mitochondrial biogenesis, mitophagy (or autophagy), and mitochondrial function under multiple physiological conditions. This may further improve our understanding of the effects of the GH–GHR–IGF1 axis on mitochondrial function, which may be controlled by the delicate balance between mitochondrial biogenesis and mitophagy. Specifically, we also highlight the challenges that remain in this field.

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Section: The Effects Of Gh–ghr–igf1 Axis On Mitochondrial Functionmentioning

confidence: 91%

Section: The Effects Of Growth Hormone Receptor On Mitochondrial Biogmentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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“…The production of reactive oxygen species (ROS) in the mitochondria of cells was measured using an ROS assay kit (Beyotime, China) according to the manufacturer's protocol. Dichlorofluorescein (DCF) fluorescence was determined using a Fluorescence/Multi-Detection Microplate Reader (BioTek, USA) as previously described [11]. Data were normalized to the control group and are expressed as a percentage of control levels.…”

Section: Detection Of Reactive Oxygen Speciesmentioning

confidence: 99%

High expression of BCL6 inhibits the differentiation and development of hematopoietic stem cells and affects the growth and development of chickens

et al. 2021

J Animal Sci Biotechnol

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Background B-cell CLL/lymphoma 6 (BCL6) is a transcriptional master regulator that represses more than 1200 potential target genes. Our previous study showed that a decline in blood production in runting and stunting syndrome (RSS) affected sex-linked dwarf (SLD) chickens compared to SLD chickens. However, the association between BCL6 gene and hematopoietic function remains unknown in chickens. Methods In this study, we used RSS affected SLD (RSS-SLD) chickens, SLD chickens and normal chickens as research object and overexpression of BCL6 in hematopoietic stem cells (HSCs), to investigate the effect of the BCL6 on differentiation and development of HSCs. Results The results showed that comparison of RSS-SLD chickens with SLD chickens, the BCL6 was highly expressed in RSS-SLD chickens bone marrow. The bone marrow of RSS-SLD chickens was exhausted and red bone marrow was largely replaced by yellow bone marrow, bone density was reduced, and the levels of immature erythrocytes in peripheral blood were increased. At the same time, the hematopoietic function of HSCs decreased in RSS-SLD chickens, which was manifested by a decrease in the hematopoietic growth factors (HGFs) EPO, SCF, TPO, and IL-3, as well as hemoglobin α1 and hemoglobin β expression. Moreover, mitochondrial function in the HSCs of RSS-SLD chickens was damaged, including an increase in ROS production, decrease in ATP concentration, and decrease in mitochondrial membrane potential (ΔΨm). The same results were also observed in SLD chickens compared with normal chickens; however, the symptoms were more serious in RSS-SLD chickens. Additionally, after overexpression of the BCL6 in primary HSCs, the secretion of HGFs (EPO, SCF, TPO and IL-3) was inhibited and the expression of hemoglobin α1 and hemoglobin β was decreased. However, cell proliferation was accelerated, apoptosis was inhibited, and the HSCs entered a cancerous state. The function of mitochondria was also abnormal, ROS production was decreased, and ATP concentration and ΔΨm were increased, which was related to the inhibition of apoptosis of stem cells. Conclusions Taken together, we conclude that the high expression of BCL6 inhibits the differentiation and development of HSCs by affecting mitochondrial function, resulting in impaired growth and development of chickens. Moreover, the abnormal expression of BCL6 might be a cause of the clinical manifestations of chicken comb, pale skin, stunted growth and development, and the tendency to appear RSS in SLD chickens.

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“…Liver tissues were fixed in 2.5% glutaraldehyde for 4 h at 4°C and then cultured as previously described (Luo et al, 2016). Transmission electron microscope (Hitachi HT7700, Japan) was used to examine and photograph mitochondria, and five randomly selected areas were photographed at × 2500 magnification and counted as previously reported (Hu et al, 2019).…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

Runting and Stunting Syndrome Is Associated With Mitochondrial Dysfunction in Sex-Linked Dwarf Chicken

Luo

et al. 2020

Front. Genet.

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Runting and stunting syndrome (RSS) in chicken are commonly known as "frozen chicken." The disease is characterized by lower body weight and slow growth and the incidence rate is widely 5%-20% in sex-linked dwarf (SLD) chickens. However, the etiology of RSS in chickens has plagued researchers for several decades. In this study, histopathology studies demonstrated that the hepatocytes of the RSS chickens contain many mitochondria with damaged and outer and inner membrane along with vacuolar hydropic degeneration. No mtDNA mutation was detected, but our microarray data showed that RSS chickens exhibited abnormal expression of genes, many of which are involved in oxidative phosphorylation (OXPHOS) and fatty acid metabolism. In particular, nuclear gene IGF2BP3 was upregulated in RSS chickens' liver cells. The abnormal expression of these genes is likely to impair the OXPHOS, resulting in reduced ATP synthesis in the hepatocytes of the RSS chickens, which may in turn leads to poor weight gain and retarded growth or stunting of chicks. Our findings suggest that mitochondria dysfunction rather than chronic inflammation is responsible for the reduced growth and RSS in SLD chickens. Mutations in GHR have been shown to compromise mitochondrial function in SLD chickens. Since the mitochondrial damage in the RSS chicken is more severe, we suggest that extra genes are likely to be affected to exacerbate the phenotype.

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Growth Hormone Receptor Gene is Essential for Chicken Mitochondrial Function In Vivo and In Vitro

Cited by 17 publications

References 40 publications

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

High expression of BCL6 inhibits the differentiation and development of hematopoietic stem cells and affects the growth and development of chickens

Runting and Stunting Syndrome Is Associated With Mitochondrial Dysfunction in Sex-Linked Dwarf Chicken

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