Downregulation of IGF-I mRNA expression during postnatal pancreatic development and overexpression after subtotal pancreatectomy and acute pancreatitis in the rat pancreas

1997 ◽  
Vol 18 (3) ◽  
pp. 233-242 ◽  
Author(s):  
E L Calvo ◽  
G Bernatchez ◽  
G Pelletier ◽  
J L Iovanna ◽  
J Morisset
Keyword(s):  
Acute Pancreatitis ◽  
Mrna Expression ◽  
Mrna Levels ◽  
Pancreatic Development ◽  
Rat Pancreas ◽  
Total Rna ◽  
Igf I ◽  
Cell Growth And Differentiation ◽  
Old Rats ◽  
Maximal Expression

ABSTRACT Insulin-like growth factors (IGFs) are important peptides involved in the regulation of cell growth and differentiation in many tissues. The ontogeny of IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26- and 70-day-old rats. For the regeneration studies two models were used: (i) 90% pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days after resection; (ii) acute pancreatitis was induced with caerulein (12μg/body weight three times a day every 8 h for 2 days) and the rats were killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was extracted by the guanidinium isothiocyanate method and Northern blots were performed using total RNA and labeled cRNA probes. Abundance of the different mRNA transcripts was estimated by densitometric scanning and normalized to the abundance of 18 S rRNA for each time point. Northern blot analysis during ontogeny showed four (0·8–1·2, 1·9, 4·7 and 7·5 kb) major transcripts in the rat pancreas and liver. Total IGF-I mRNA was 40-fold higher in the adult liver than in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in the adult than in the fetus, whereas in the pancreas, the highest levels were observed around birth. During the first 3 days after pancreatectomy, a peak of maximal expression was observed after the second day. Densitometric analysis of each IGF-I mRNA species showed concomitant increases in all transcripts. After 6 days, all transcripts had returned to near-control values. IGF-I mRNA expression 2 days after pancreatectomy was 3·5-fold higher than in the newborn. During the first 2 days of acute pancreatitis induction, overexpression of IGF-I mRNA was observed. However, soon after the second day of caerulein treatment, the 7·5 kb transcripts remained elevated whereas those of the others regressed toward control values. Our results show that IGF-I mRNA is overexpressed in both models of pancreatic regeneration but downregulated in the normal adult pancreas.

scholarly journals Effect of IGF-I and PDGF administered in vivo on the expression of osteoblast-related genes in old rats

2002 ◽  
Vol 174 (1) ◽  
pp. 63-70 ◽  
Author(s):  
H Tanaka ◽  
A Wakisaka ◽  
H Ogasa ◽  
S Kawai ◽  
CT Liang
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Mrna Expression ◽  
Combined Treatment ◽  
Mrna Levels ◽  
Adult Rats ◽  
Igf I ◽  
Old Rats ◽  
Osteoblast Markers ◽  
Marrow Ablation

In order to establish the cellular basis for using growth factors as possible therapeutic agents for the age-dependent deficit in bone formation activity, we examined the individual and combined effects of IGF-I and/or platelet-derived growth factor (PDGF) on the gene expression of osteoblast-related markers in male rats. The expression of osteoblast markers was examined in the femurs of adult and old rats following marrow ablation, which amplifies gene expression activity. The mRNA levels of collagen(alpha1) (I) (COLI), alkaline phosphatase (AP), osteopontin (OP) and osteocalcin (OC) were significantly lower in the old as compared with the adult rats. To determine whether growth factors can abolish the age-related deficits in mRNA expression in old bone, PDGF and/or IGF-I were infused directly into the right femur for 5 days following marrow ablation. The contralateral femur was infused with vehicle only and used as a control. PDGF stimulated the expression of OP mRNA in both adult and old rats, whereas COLI, AP and OC mRNAs were not affected. IGF-I infusion did not have a significant effect on mRNA expression in adult rats. In contrast, treatment with IGF-I significantly enhanced the mRNA levels of COLI, AP and OP in old rats. To examine whether the combination of both factors could affect the expression of osteoblast markers synergistically, PDGF and IGF-I were infused together. In adult bones, the combined treatment with PDGF and IGF-I caused a slight increase in the level of OP gene expression but no change in AP, OC or COLI genes. Although neither IGF-I nor PDGF alone was effective in stimulating the expression of OC, the combined treatment in old bones enhanced OC expression significantly. The expression of COLI, AP and OP was also stimulated, but the stimulation was no different from that of IGF-I alone. In PDGF plus IGF-I treatment with a high dose, no dose-response effects were observed. Within the limits of the present study, it is suggested that IGF-I and, to a much lesser extent, PDGF may partially restore the deficit in the expression of osteoblast markers in old bones, and that the combination of both factors is slightly better than IGF-I alone in stimulating OC expression.

Tumor necrosis factor inhibits growth hormone-mediated gene expression in hepatocytes

2006 ◽  
Vol 291 (1) ◽  
pp. G35-G44 ◽  
Author(s):  
Tamer Ahmed ◽  
Gladys Yumet ◽  
Margaret Shumate ◽  
Charles H. Lang ◽  
Peter Rotwein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Protein Tyrosine Phosphatases ◽  
Mrna Levels ◽  
Inhibitory Effects ◽  
Protein Levels ◽  
Mrna Induction ◽  
Igf I

Growth hormone (GH) stimulates STAT5 phosphorylation by JAK2, which activates IGF-I and serine protease inhibitor 2.1 (Spi 2.1) transcription, whereas STAT5 dephosphorylation by protein tyrosine phosphatases (PTPs) terminates this signal. We hypothesized that the inhibitory effects of TNF on GH signaling and gene transcription were responsible for hepatic GH resistance. CWSV-1 hepatocytes were treated with TNF, pervanadate (a PTP inhibitor), or both, before GH stimulation. Total and tyrosine-phosphorylated JAK2, STAT5, ERK1/2, SHP-1 and SHP-2, IGF-I, and Spi 2.1 mRNA levels were measured. GH stimulated STAT5 and ERK1/2 phosphorylation, IGF-I, and Spi 2.1 mRNA expression. TNF attenuated JAK2/STAT5 and ERK1/2 phosphorylation and IGF-I and Spi 2.1 mRNA expression following GH stimulation. SHP-1 and SHP-2 protein levels were unaltered by TNF or GH, and the GH-induced increase in SHP-1 PTP activity was not further increased by TNF. In TNF-treated cells, pervanadate restored STAT5 and ERK1/2 phosphorylation to control levels following GH stimulation but did not restore IGF-I or Spi 2.1 mRNA induction. Cells transfected with a Spi 2.1 promoter-luciferase vector demonstrate a 50-fold induction in luciferase activity following GH stimulation or cotransfection with a constitutively active STAT5 vector. TNF prevented the induction of Spi 2.1 promoter activity by GH and the STAT5 construct. We conclude that TNF does not inhibit GH activity by inducing SHP-1 or -2 expression and that correction of GH signaling defects in TNF-treated cells by pervanadate does not restore GH-induced gene expression. The inhibitory effects of TNF on GH-mediated gene transcription appear independent of STAT5 activity and previously identified abnormalities in JAK2/STAT5 signaling.

IGFBP mRNA expression in small intestine of rat during postnatal development

2001 ◽  
Vol 281 (6) ◽  
pp. G1378-G1384 ◽  
Author(s):  
C. A. Shoubridge ◽  
C.-B. Steeb ◽  
L. C. Read
Keyword(s):  
Mrna Expression ◽  
Postnatal Development ◽  
Age Groups ◽  
Rat Intestine ◽  
Age Related ◽  
Igf I ◽  
Igf Binding ◽  
Old Rats ◽  
Igf Binding Protein ◽  
Igfbp 3

In contrast to the adult gut, the immature intestine is refractory to subcutaneously infused insulin-like growth factor I (IGF-I). IGF binding protein (IGFBP) mRNA expression was characterized in intestinal tissues from 6-, 19-, and 90-day-old rats to determine if changes in local expression could account for this age-related change in IGF-I potency. For all age groups, IGFBP-3 to -6, but not IGFBP-1 or -2, were detected by Northern blot analysis. IGFBP-3, -4, and -5 were more intensely expressed in the 6-day-old rat intestine compared with weanling or adult tissue. In contrast, IGFBP-6 expression peaked at the time of weaning. In situ hybridization showed IGFBP-3 to -6 expression was confined to cells of the lamina propria and submucosa and also in the muscularis layer for IGFBP-5. Furthermore, the pattern of IGFBP-5 localization in the intestine changed with development. The findings indicate that the expression of IGFBP-3 to -6 is higher in the immature intestine compared with the adult intestine, suggesting locally produced IGFBPs may inhibit systemically derived IGF-I action in the intestine. Therefore, changes to local IGFBP expression may contribute to the varying response of the rat intestine to IGF-I peptides during postnatal development.

Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats

1997 ◽  
Vol 272 (3) ◽  
pp. E453-E460 ◽  
Author(s):  
C. Duchamp ◽  
K. A. Burton ◽  
A. Geloen ◽  
M. J. Dauncey
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Unit Weight ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Total Rna ◽  
Brown Adipose ◽  
Igf I

The possible involvement of locally produced insulin-like growth factor I (IGF-I) in the cold-induced hyperplasia of interscapular brown adipose tissue (BAT) was investigated in 2-, 4-, and 7-day cold-exposed (CE, 4 degrees C) rats by measuring BAT IGF-I expression at a time when extensive BAT cell proliferation occurs. By comparison with thermoneutral (25 degrees C) controls, plasma IGF-I decreased in CE rats despite an increased food intake, whereas BAT IGF-I peptide increased markedly to peak after 4 days at 4 degrees C. The ratio of class 1 to class 2 IGF-I mRNA was much higher in BAT than in liver. BAT IGF-I mRNA levels per unit weight total RNA doubled after 2 days at 4 degrees C but decreased thereafter to the level in controls. Upregulation of BAT IGF-I mRNA also occurred in CE rats with a food intake restricted to the level of controls. The transient cold-induced upregulation of BAT IGF-I (per unit weight total RNA) suggests that IGF-I plays a role in the early cold-induced BAT hyperplasia that occurs in vivo.

scholarly journals Vascular Endothelial Injury and Apoptosis in Rats with Severe Acute Pancreatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ning Ge ◽  
Qing Xia ◽  
Zhong-Hua Yang ◽  
Qun-Fang Ding ◽  
Zhi Zeng
Keyword(s):  
Acute Pancreatitis ◽  
Mrna Expression ◽  
Severe Acute Pancreatitis ◽  
Endothelial Injury ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Endothelial Protein C Receptor ◽  
Necrosis Factor Alpha ◽  
Experimental Group ◽  
Aortic Endothelial

We explored mechanisms of vascular endothelial injury that lead to systemic multiple organ failure by detecting the soluble endothelial protein C receptor (sEPCR), von Willebrand factor (vWF), serum nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) and Bcl-2 mRNA and Bax mRNA expression in a severe acute pancreatitis (SAP) rat model. Compared to controls, the levels of TNF-α, vWF, and sEPCR were significantly increased in the experimental group at 12 hours and 24 hours and the NO level was significantly decreased. After 12 hours, the aortic endothelial apoptosis index and Bax mRNA expression in aortic endothelial cells had increased in the experimental group, but Bcl-2 mRNA levels had decreased. All these changes appeared at both 12 h and 24 hours. The results indicated that vascular endothelial injury and apoptosis markers were elevated in SAP. Endothelial injury and increased apoptosis in the experimental group were related to the increased expression of TNF-α.

IGF-I downregulates resistin gene expression and protein secretion

2005 ◽  
Vol 288 (5) ◽  
pp. E1019-E1027 ◽  
Author(s):  
Yen-Hang Chen ◽  
Pei-Fang Hung ◽  
Yung-Hsi Kao
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Mrna Expression ◽  
P38 Mapk ◽  
Protein Secretion ◽  
Protein Release ◽  
Mrna Levels ◽  
Igf I ◽  
Phosphoinositide 3 Kinase ◽  
Sb 203580

Resistin (Rstn) is known as an adipocyte-specific secretory factor that can cause insulin resistance and decrease adipocyte differentiation. Conversely, based on various studies, insulin-like growth factors (IGFs) can improve insulin resistance and stimulate adipocyte adipogenesis. Whether IGFs exert their effects through the control of Rstn's production or modulation of Rstn's action is unknown. This study was designed to examine the influence and the signaling of IGF-I on Rstn gene expression and protein secretion by 3T3-L1 adipocytes. We found that IGF-I suppressed Rstn mRNA expression and protein release in dose- and time-dependent manners. The IC50 of IGF-I was ∼1 nM for a range of 6–10 h of treatment. Treatment with cycloheximide, but not with actinomycin D, prevented IGF-I-suppressed Rstn mRNA expression, suggesting that IGF-I destabilizes Rstn mRNA and that IGF-I's effect requires new protein, but not mRNA, synthesis. Pretreatment with IGF-I receptor (IGF-IR) antibody blocked IGF-I-altered IGF-IR activity and Rstn mRNA levels. Neither PD-98059, SB-203580, nor LY-294002 changed the IGF-I-decreased levels of Rstn mRNA, but they inhibited IGF-I-stimulated activities of MEK1, p38 MAPK, and phosphoinositide 3-kinase, respectively. However, SB-203580 antagonized the IGF-I-decreased Rstn protein release. These data demonstrate that IGF-I downregulates Rstn gene expression via IGF-IR-dependent and MEK1-, p38 MAPK-, and phosphoinositide 3-kinase-independent pathways and likely modifies the distribution of Rstn protein between the intracellular and extracellular compartments via a p38 MAPK-dependent pathway. Decreases in Rstn production and secretion induced by IGF-I may be related to the mechanism by which IGF-I modulates body weight and diabetes in animals.

In vivo and in vitro effects of insulin-like growth factor-I (IGF-I) on femoral mRNA expression in old rats

Bone ◽  
1994 ◽  
Vol 15 (6) ◽  
pp. 647-653 ◽  
Author(s):  
H. Tanaka ◽  
R. Quarto ◽  
S. Williams ◽  
J. Barnes ◽  
C.T. Liang
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Old Rats ◽  
Growth Factor I ◽  
In Vitro Effects

scholarly journals Analysis of Chemokines and Receptors Expression Profile in the Myelin MutantTaiepRat

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Guadalupe Soto-Rodriguez ◽  
Juan-Antonio Gonzalez-Barrios ◽  
Daniel Martinez-Fong ◽  
Victor-Manuel Blanco-Alvarez ◽  
Jose R. Eguibar ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profile ◽  
Proinflammatory Cytokines ◽  
Mrna Levels ◽  
Pcr Array ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Chronic Neuroinflammation ◽  
Sprague Dawley Rats ◽  
Old Rats

Taieprat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-oldtaieprats. We used a Rat RT2Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in thetaieprat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in thetaieprat.

Expression of the Thrombopoietin Gene in Human Fetal and Neonatal Tissues

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Eva-Maria Wolber ◽  
Christof Dame ◽  
Hubert Fahnenstich ◽  
Dietmar Hofmann ◽  
Peter Bartmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mrna Expression ◽  
Blood Platelet ◽  
Preterm Neonates ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fetal Life ◽  
Mrna Levels ◽  
Human Fetuses ◽  
Total Rna ◽  
Polymerase Chain

Thrombopoietin (TPO) regulates megakaryopoiesis and platelet production. In the adult, TPO is mainly produced by the liver and the kidneys. This study focuses on fetal and neonatal TPO mRNA expression. In 26 human fetuses and preterm neonates, samples from liver, kidney, spleen, lung, and bone marrow were extracted for total RNA. We measured platelet counts, TPO serum concentrations by enzyme-linked immunosorbent assay, and TPO mRNA contents by reverse transcription/competitive polymerase chain reaction. TPO mRNA concentrations per microgram total RNA were similar in liver, spleen, and bone marrow, slightly lower in kidney, and significantly lower in lung. When related to gram tissue, TPO mRNA levels were highest in the liver. Considering the total amount of TPO mRNA produced in liver, kidney, and spleen, the liver accounted for 95.3%. No correlations between TPO mRNA expression and serum TPO concentration, blood platelet count, or gestational age were observed. In conclusion, the liver is the primary site of TPO gene expression in human fetuses and neonates. The spleen may contribute to TPO production during fetal life. Like in the adult, TPO mRNA is expressed in fetal bone marrow.

Fatty acid transport protein-1 mRNA expression in skeletal muscle and in adipose tissue in humans

2000 ◽  
Vol 279 (5) ◽  
pp. E1072-E1079 ◽  
Author(s):  
Christophe Binnert ◽  
Heikki A. Koistinen ◽  
Geneviève Martin ◽  
Fabrizio Andreelli ◽  
Pertti Ebeling ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Mrna Expression ◽  
Mrna Levels ◽  
Total Rna ◽  
Fatty Acid Transporter ◽  
Acid Transporter ◽  
Type 2 Diabetic

Fatty acid transporter protein (FATP)-1 mRNA expression was investigated in skeletal muscle and in subcutaneous abdominal adipose tissue of 17 healthy lean, 13 nondiabetic obese, and 16 obese type 2 diabetic subjects. In muscle, FATP-1 mRNA levels were higher in lean women than in lean men (2.2 ± 0.1 vs. 0.6 ± 0.2 amol/μg total RNA, P < 0.01). FATP-1 mRNA expression was decreased in skeletal muscle in obese women both in nondiabetic and in type 2 diabetic patients ( P < 0.02 vs. lean women in both groups), and in all women there was a negative correlation with basal FATP-1 mRNA level and body mass index ( r = −0.74, P < 0.02). In men, FATP-1 mRNA was expressed at similar levels in the three groups both in skeletal muscle (0.6 ± 0.2, 0.6 ± 0.2, and 0.8 ± 0.2 amol/μg total RNA in lean, obese, and type 2 diabetic male subjects) and in adipose tissue (0.9 ± 0.2 amol/μg total RNA in the 3 groups). Insulin infusion (3 h) reduced FATP-1 mRNA levels in muscle in lean women but not in lean men. Insulin did not affect FATP-1 mRNA expression in skeletal muscle in obese nondiabetic or in type 2 diabetic subjects nor in subcutaneous adipose tissue in any of the three groups. These data show a gender-related difference in the expression of the fatty acid transporter FATP-1 in skeletal muscle of lean individuals and suggest that changes in FATP-1 expression may not contribute to a large extent to the alterations in fatty acid uptake in obesity and/or type 2 diabetes.

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