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1.
Trop Anim Health Prod ; 53(4): 413, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34308489

RESUMO

Leptin an adipokine plays a significant role in several physiological processes and has been indicated as a candidate gene for marker-assisted selection for high-yielding cows. Insulin-like growth factor-1 (IGF-1) hormone plays an important physiological role in growth, development, metabolism, and lactation in bovines. It is believed to be one of the main mediators of energy balance effects on the reproductive performance of dairy cows after calving. The present investigation was carried out to identify the novel polymorphisms in exon 3 region of leptin and exon 3 partial intron 3 of IGF-1 genes and their association with the milk production performance in indicine and taurine crossbred (Karan Fries) cows. Blood samples were collected from 160 apparently healthy Karan Fries (KF) cows. Four SNPs (single-nucleotide polymorphisms) at positions rs29004508 (C > T), rs29004509 (C > T), rs29004510 (T > C), and rs29004511 (T > C) in leptin gene and two SNPs at positions rs133251968 (C > A) and rs137289661 (C > T) in IGF-1 gene were found in KF cows; however, rs29004509 (C > T) had a positive correlation (r = 0.376; P < 0.05) with milk yield. The genetic variants observed in exon 3 region of leptin gene and their association with milk yield traits revealed the importance of CT genotype, which had been useful for genetic improvement of KF cow for milk production traits and can also be utilized as a potential genetic marker to select appropriate animals.


Assuntos
Leptina , Leite , Animais , Bovinos/genética , Feminino , Fator de Crescimento Insulin-Like I/genética , Lactação , Leptina/genética , Polimorfismo de Nucleotídeo Único , Alcaloides de Pirrolizidina , Taurina
2.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208601

RESUMO

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-ß1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.


Assuntos
Metabolismo dos Carboidratos , Neoplasias Colorretais/metabolismo , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/terapia , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/prevenção & controle , Fatores de Risco
3.
World J Surg Oncol ; 19(1): 207, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253194

RESUMO

BACKGROUND: Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. METHODS: Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. RESULTS: IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. CONCLUSIONS: The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Apoptose , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , MicroRNAs/genética , Prognóstico , Neoplasias do Colo do Útero/genética
4.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201855

RESUMO

The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet-gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (ß = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (ß = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.


Assuntos
Ácidos/metabolismo , Dieta , Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único/genética , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Característica Quantitativa Herdável , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interleucina-6/genética , Rim/metabolismo , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade
5.
Eur J Endocrinol ; 185(2): 323-332, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34125705

RESUMO

Context: Short stature in children is a common reason for referral to pediatric endocrinologists. The underlying cause of short stature remains unclear in many cases and patients often receive unsatisfactory, descriptive diagnoses. While textbooks underline the rarity of genetic causes of growth hormone (GH) insensitivity and the severity of its associated growth failure, increased genetic testing in patients with short stature of unclear origin has revealed gene defects in the GH/insulin-like growth factor (IGF-I) axis associated with milder phenotypes. As such, heterozygous IGF1 gene defects have been reported as a cause of mild and severe short stature. Here, we aimed to describe the clinical and hormonal profile of children with IGF1 haploinsufficiency and their short-term response to growth hormone treatment (GHT). Case descriptions: We describe five patients presenting with short stature, microcephaly, and in four out of five born small for gestational age diagnosed with IGF1 haploinsufficiency. The phenotype of these patients resembles that of previously described cases with similar gene defects. In our series, segregation of the short stature with the IGF1 deletion is evident from the pedigrees and our data suggests a modest response to GHT. Conclusions: This study is the first case series of complete heterozygous IGF1 deletions in children. The specific genetic defects provide a clear image of the phenotype of IGF1 haploinsufficiency - unbiased by heterozygous mutations with possible dominant negative effects on IGF-I function. We increase the evidence for IGF1 haploinsufficiency as a cause of short stature, microcephaly, and SGA.


Assuntos
Nanismo/diagnóstico , Nanismo/genética , Haploinsuficiência/genética , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Fator de Crescimento Insulin-Like I/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Linhagem
6.
Theriogenology ; 169: 56-64, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33933758

RESUMO

IGF-1 plays important roles in mammalian fertility by promoting cell growth and increasing steroid hormone secretion. Although IGF-1 significantly upregulated luteinizing hormone/choriogonadotropin receptor (LHCGR) gene expression in granulosa cells in a previous study, the mechanism was unclear. The present experiment was designed to primarily explore the regulation of LHCGR expression by IGF-1. First, based on a porcine LHCGR double-luciferase reporter experiment, c-Fos significantly inhibited the activity of the LHCGR promoter. Second, porcine granulosa cells were cultured in vitro with IGF-1, and we observed that the expression of LHCGR was significantly increased and the expression of c-Fos mRNA significantly reduced. After c-Fos overexpression in granulosa cells, IGF-1 attenuated the inhibitory effect of c-Fos on LHCGR. Furthermore, the level of LHCGR mRNA stimulated by IGF-1 in the presence of SB203580 was markedly lower than that of IGF-1 alone action. In conclusion, IGF-1 enhanced the expression of LHCGR by regulating c-Fos in granulosa cells, which may be mediated by the p38MAPK-signaling pathway.


Assuntos
Hormônio Foliculoestimulante , Fator de Crescimento Insulin-Like I , Receptores do LH/genética , Animais , Células Cultivadas , Feminino , Células da Granulosa , Fator de Crescimento Insulin-Like I/genética , RNA Mensageiro/genética , Suínos
7.
Sheng Wu Gong Cheng Xue Bao ; 37(4): 1249-1259, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33973439

RESUMO

The aim of this study was to investigate the expression of growth hormone (GH) gene on skeletal muscle cell proliferation of Guizhou cattle. The coding sequence of cattle GH gene was amplified by reverse transcription PCR, cloned into the pUCM-T vector and then used to construct the GH gene overexpression vector pEGFP-N3-GH. The expression of the GH gene in skeletal muscle-related tissues (psoas major and longissimus dorsi) of Guizhou cattle was determined by real-time fluorescent quantitative PCR (RT-qPCR). This was followed by culturing and identification of the bovine primary skeletal muscle cells. Subsequently, we introduced the GH gene overexpression vector into the cells to investigate its effect on the proliferation of bovine skeletal muscle cells and the expression of insulin like growth factor 1 and 2 genes related to skeletal muscle growth and development. RT-qPCR results showed that the expression level of GH gene was higher in the psoas major than in the longissimus dorsi of Guizhou cattle, and the expression level in the psoas major of Guanling cattle and Weining cattle was significantly higher than in the longissimus dorsi (P<0.05). The transfection and proliferation results showed that pEGFP-N3-GH significantly increased the expression of GH, IGF-1, and IGF-2 genes in skeletal muscle cells compared to pEGFP-N3 (PP<0.05), and that overexpression of the GH gene also significantly increased the proliferation rate of skeletal muscle cells at the four periods examined (PP<0.01). Our results suggest that GH gene can promote the proliferation of skeletal muscle cells of Guizhou cattle and exerts a positive regulatory effect. This lays the foundation for further exploring the mechanism by which the GH gene affects the growth and development of Guizhou cattle.


Assuntos
Hormônio do Crescimento , Fator de Crescimento Insulin-Like I , Animais , Bovinos , Proliferação de Células , Clonagem Molecular , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Músculo Esquelético
8.
J Med Food ; 24(5): 497-504, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34009019

RESUMO

Previously, we reported that the administration of a mixture of Humulus japonicus (MH) increased the longitudinal bone growth rate in Sprague Dawley rats. In this study, we investigated the effects of the dietary administration of MH on longitudinal bone growth in growth hormone (GH)-deficient hypophysectomized male and female rats to determine whether the effect of MH was similar to that of GH. We measured the nose-to-anus and nose-to-tail length gain, femur and tibia lengths, growth plate zones, and expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) after the dietary administration of MH or the injection of GH into hypophysectomized rats for 4 weeks. Results demonstrated that the dietary administration of MH had no effect on longitudinal bone growth, whereas the injection of GH increased the nose-to-tail length gain and femur and tibia lengths in hypophysectomized rats. In addition, MH did not affect the growth plate, bone mineralization, and expression of IGF-1 and IGFBP-3. These findings indicate that MH does not exert a GH-like effect and that the effects of MH and GH on longitudinal bone growth involve different pathways.


Assuntos
Humulus , Animais , Desenvolvimento Ósseo , Feminino , Hormônio do Crescimento , Hipofisectomia , Fator de Crescimento Insulin-Like I/genética , Masculino , Ratos , Ratos Sprague-Dawley
9.
Aging (Albany NY) ; 13(9): 12631-12640, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33910166

RESUMO

BACKGROUND: Obesity is an important part of polycystic ovary syndrome (PCOS) pathologies. The present study utilized the bioinformatics method to identify the molecular mechanism of obesity status in PCOS. METHODS: Six transcriptome profiles of adipose tissue were obtained from online databases. The background correction and normalization were performed, and the DEGs were detected with the settings p < 0.05. The GO, KEGG pathway enrichment, and PPI network analysis were performed with the detected DEGs. RESULTS: A total of 37 DGEs were found between obesity PCOS and healthy controls, and 8 of them were tested significant in the third database. The expression patterns of the 8 detected DGEs were then measured in another two datasets based on lean/obesity PCOS patients and healthy controls. The gene CHRDL1 was found to be in linear regression with the BMI index in PCOS patients (p = 0.0358), but such a difference was not found in healthy controls (p = 0.2487). The expression of CHRDL1 was significantly higher in obesity PCOS cases than the BMI matched healthy controls (p = 0.0415). Further enrichment research demonstrated the CHRDL1 might function as an inhibitor of the BMP4 or IGF1 signalling. CONCLUSION: In summary, the present study identified CHRDL1 as a candidate gene responsible for the obesity of PCOS patients.


Assuntos
Obesidade/genética , Obesidade/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Índice de Massa Corporal , Proteína Morfogenética Óssea 4/genética , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Feminino , Humanos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
10.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804803

RESUMO

Cachexia causes high mortality, low quality of life, and rapid weight loss in cancer patients. Sarcopenia, a condition characterized by the loss of muscle, is generally present in cachexia and is associated with inflammation. M2 macrophages, also known as an anti-inflammatory or alternatively activated macrophages, have been shown to play a role in muscle repair. Magnoliae Cortex (M.C) is a widely used medicinal herb in East Asia reported to have a broad range of anti-inflammatory activities; however, the effects of M.C on sarcopenia and on M2 macrophage polarization have to date not been studied. This study was designed to investigate whether the oral administration of M.C could decrease cisplatin-induced sarcopenia by modulating M2 macrophage polarization in mice. C57BL/6 mice were injected intraperitoneally with cisplatin (2.5 mg/kg) to mimic chemotherapy-induced sarcopenia. M.C extract (50, 100, and 200 mg/kg) was administered orally every 3 days (for a total of 12 times). M.C (100 and 200 mg/kg) significantly alleviated the cisplatin-induced loss of body mass, skeletal muscle weight, and grip strength. In addition, M.C increased the expression of M2 macrophage markers, such as MRC1, CD163, TGF-ß, and Arg-1, and decreased the expression of M1-specific markers, including NOS2 and TNF-α, in skeletal muscle. Furthermore, the levels of like growth factor-1(IGF-1), as well as the number of M2a and M2c macrophages, significantly increased in skeletal muscle after M.C administration. M.C did not interfere with the anticancer effect of cisplatin in colon cancer. Our results demonstrated that M.C can alleviate cisplatin-induced sarcopenia by increasing the number of M2 macrophages. Therefore, our findings suggest that M.C could be used as an effective therapeutic agent to reverse or prevent cisplatin-induced sarcopenia.


Assuntos
Cisplatino/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Magnolia/química , Atrofia Muscular/metabolismo , Extratos Vegetais/farmacologia , Sarcopenia/etiologia , Sarcopenia/metabolismo , Animais , Biomarcadores , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Extratos Vegetais/química , Sarcopenia/tratamento farmacológico , Sarcopenia/patologia
11.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919940

RESUMO

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.


Assuntos
Reabsorção Óssea/genética , Fator de Crescimento Insulin-Like I/genética , Osteogênese/efeitos dos fármacos , Proteína Plasmática A Associada à Gravidez/genética , Animais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/genética , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/patologia , Proteínas de Transporte/genética , Colágeno Tipo I/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos , Camundongos Knockout , Osteocalcina/genética , Osteopontina/genética , Caracteres Sexuais
12.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799501

RESUMO

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Leptina/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Metabolismo Energético/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hormônio do Crescimento/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intraventriculares , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Somatostatina/genética , Somatostatina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
13.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799503

RESUMO

Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory pathway. In addition, GH deficiency conditions hearing loss or central auditory processing disorders. There are promising animal studies that reflect a possible regenerative role when exogenous GH is used in hearing impairments, demonstrated in in vivo and in vitro studies, and also, even a few studies show beneficial effects in humans presented and substantiated in the main text, although they should not exaggerate the main conclusions.


Assuntos
Vias Auditivas/metabolismo , Hormônio do Crescimento/genética , Perda Auditiva Funcional/genética , Perda Auditiva Neurossensorial/genética , Hipocampo/metabolismo , Fator de Crescimento Insulin-Like I/genética , Animais , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Vias Auditivas/patologia , Cóclea/metabolismo , Cóclea/patologia , Nervo Coclear/metabolismo , Nervo Coclear/patologia , Regulação da Expressão Gênica , Hormônio do Crescimento/metabolismo , Perda Auditiva Funcional/metabolismo , Perda Auditiva Funcional/fisiopatologia , Perda Auditiva Neurossensorial/metabolismo , Perda Auditiva Neurossensorial/fisiopatologia , Hipocampo/patologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Regeneração Nervosa/fisiologia , Ruído/prevenção & controle
14.
Am J Respir Cell Mol Biol ; 64(5): 617-628, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33689672

RESUMO

Skeletal muscle dysfunction is one of the important comorbidities of chronic obstructive pulmonary disease (COPD); however, the underlying mechanisms remain largely unknown. RANKL (receptor activator of nuclear factor κB ligand), a key mediator in osteoclast differentiation, was also found to play a role in skeletal muscle pathogenesis. Whether RANKL is involved in COPD-related skeletal muscle dysfunction is as-of-yet unknown. We examined the expression of RANKL/RANK in skeletal muscles from mice exposed to cigarette smoke (CS) for 24 weeks. Grip strength and exercise capacity as well as muscular morphology were evaluated in CS-exposed mice with or without anti-RANKL treatment. The expressions of protein synthesis- or muscle growth-related molecules (IGF-1, myogenin, and myostatin), muscle-specific ubiquitin E3 ligases (MuRF1 and atrogin-1), and the NF-κb inflammatory pathway were also evaluated in skeletal muscles. The effect of CS extract on RANKL/RANK expression and that of exogenous RANKL on the ubiquitin-proteasome pathway in C2C12 myotubes were investigated in vitro. Long-term CS exposure induced skeletal muscle dysfunction and atrophy together with upregulation of RANKL/RANK expression in a well-established mouse model of COPD. RANKL neutralization prevented skeletal muscle dysfunction and atrophy. RANKL inhibition decreased expressions of myostatin and MuRF1/Atrogin1 and suppressed the NF-κb pathway in skeletal muscles from CS-exposed mice. In in vitro experiments with C2C12 myotubes, CS extract induced expression of RANKL/RANK, and exogenous RANKL induced activation of the ubiquitin-proteasome pathway and NF-κb pathway via RANK. Our results revealed an important role of the RANKL/RANK pathway in muscle atrophy induced by CS exposure, suggesting that RANKL may be a potential therapeutic target in COPD-related skeletal muscle dysfunction.


Assuntos
Atrofia Muscular/genética , NF-kappa B/genética , Doença Pulmonar Obstrutiva Crônica/genética , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Animais , Anticorpos Neutralizantes/farmacologia , Linhagem Celular , Fumar Cigarros/efeitos adversos , Misturas Complexas/antagonistas & inibidores , Misturas Complexas/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Força da Mão/fisiologia , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Força Muscular/efeitos dos fármacos , Força Muscular/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Miogenina/genética , Miogenina/metabolismo , Miostatina/genética , Miostatina/metabolismo , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
15.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672678

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein-protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.


Assuntos
Fibrose Pulmonar Idiopática/genética , Anexina A3/genética , Colágeno Tipo I/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Cadeias beta de Integrinas/genética , Metaloproteinases da Matriz/genética , Osteopontina/genética , Mapas de Interação de Proteínas , Proteínas Qa-SNARE/genética , Trombospondinas/genética
16.
Zhongguo Gu Shang ; 34(3): 275-81, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787175

RESUMO

OBJECTIVE: To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein. METHODS: Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot. RESULTS: In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (P<0.05). (2) Compared with YC group, the increase of the expression of IGF-I mRNA in YEA group was more obvious(P=0.051). (3)The expression of p-Akt and p-mTOR in YA group was significantly higher than that in YC group (P<0.05), and the expressionof p-mTOR, p-p70S6K also showed an increasing trend in YEA group (P>0.05). CONCLUSION: Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.


Assuntos
Eletroacupuntura , Envelhecimento , Animais , Exercício Físico , Fator de Crescimento Insulin-Like I/genética , Masculino , Músculo Esquelético , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley
17.
Nat Commun ; 12(1): 1789, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741976

RESUMO

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.


Assuntos
Envelhecimento , Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Flagelos/metabolismo , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Animais Geneticamente Modificados , Transporte Biológico , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Longevidade/genética , Percepção/fisiologia , Interferência de RNA , Fator Regulador X1/genética , Fator Regulador X1/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Environ Toxicol ; 36(6): 1195-1205, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33720504

RESUMO

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose-depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF-1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p < .05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p < .05), suggesting that ammonia exposure could perturb both GH/IGF-axis and HPT-axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase-polypeptide 1(s6k1) in the dorsal muscle were significantly down-regulated in the fish exposed to ammonia (p < .05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress.


Assuntos
Amônia , Somatomedinas , Amônia/toxicidade , Animais , Regulação para Baixo , Hormônio do Crescimento , Fator de Crescimento Insulin-Like I/genética , Fosfatidilinositol 3-Quinases
19.
Environ Toxicol Pharmacol ; 84: 103613, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33571669

RESUMO

To explore the relationship of oxidative stress and TGF-ß 1/Smad3 pathway in the inhibition of osteoblast mineralization by copper chloride (CuCl2), the osteoblasts were treated with CuCl2 (0, 50 µM, 100 µM, 150 µM CuCl2 5H2O) for 24 h. We found that Cu impaired the osteoblast structure, inhibited the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, alkaline phosphatase (ALP) content, mRNA expression of collagen I (COL-I), osteocalcin (OCN), insulin-like growth factor I (IGF-I), bone morphogenetic protein-2 (BMP-2), transforming growth factor ß1 (TGF-ß1) and core-binding factor α1 (Cbfα1), promoted the reactive oxygen species (ROS) production, inactivated the TGF-ß1/Smad3 pathway. It indicates that the inactivated TGF-ß1/Smad3 pathway leads to osteoblast impairment by CuCl2. It will contribute to clarify the influence of CuCl2 on the osteoblast mineralization.


Assuntos
Cobre/toxicidade , Osteoblastos/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/genética , Calcificação Fisiológica , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Fator de Crescimento Insulin-Like I/genética , Osteoblastos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/genética
20.
Poult Sci ; 100(2): 467-473, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518098

RESUMO

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.


Assuntos
Embrião de Galinha/efeitos da radiação , Somatotrofos/metabolismo , Animais , Embrião de Galinha/química , Hormônio do Crescimento/sangue , Hormônio Liberador de Hormônio do Crescimento/análise , Hormônios/análise , Hormônios/sangue , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Luz , Fígado/química , Óvulo/efeitos da radiação , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Somatotrofos/efeitos da radiação , Fatores de Tempo
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