Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats

Park, In-Soek; Kiyomoto, Hideyasu; Alvarez, Flavio; Xu, Yichun; Abboud, Hanna E.; Abboud, Sherry L.

doi:10.1016/s0272-6386(98)70075-7

Cited by 27 publications

(34 citation statements)

References 40 publications

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“…In vitro transcription was performed using the Riboprobe System II kit (Promega) according to the manufacturer's instructions. ISH was carried out as we have previously described (Park et al 1998). Serial sections of tissues hybridized under identical conditions with the sense probe served as negative controls.…”

Section: Ish Of Non-transgenic Tissuesmentioning

confidence: 99%

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹

Abboud

Bunegin

Ghosh‐Choudhury

et al. 2003

J Histochem Cytochem.

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S U M M A R Y CSF-1 stimulates monocyte and osteoclast populations. However, the molecular mechanisms involved in regulating CSF-1 gene expression are unclear. To identify regulatory regions that control normal CSF-1 gene expression, a Ϫ 774/ ϩ 183-bp fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo. Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA compared to ARH-77 B cells that lack CSF-1 gene expression. Transient transfection of osteoblasts with promoter deletion constructs showed that the Ϫ 774-bp fragment conferred the highest transcriptional activity and contained activator and repressor sequences. To assess the ability of the CSF-1 promoter to confer normal tissue expression of CSF-1, transgenic mice containing the Ϫ 774/ ϩ 183-bp region driving the E. coli ␤ -galactosidase (lacZ) reporter gene were generated. ␤ -Gal analysis of whole tissue extracts showed transgene expression in all tissues tested except liver and kidney. At the cellular level, the pattern of ␤ -gal expression in the spleen, thymus, bone, lung, and testes of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non-transgenic littermates detected by in situ hybridization. This region also directed appropriate transgene expression to sites in other tissues known to synthesize CSF-1, with the exception of the liver and kidney. These findings indicate that the Ϫ 774-bp fragment contains cis -acting elements sufficient to direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be useful for studying the transcriptional mechanisms involved in regulating CSF-1 gene expression in tissues throughout development.

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Section: Ish Of Non-transgenic Tissuesmentioning

confidence: 99%

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹

Abboud

Bunegin

Ghosh‐Choudhury

et al. 2003

J Histochem Cytochem.

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“…The kidney expresses all six IGFBPs, of which IGFBP-1 and IGFBP-2 have been observed to exhibit increased tissue levels during the onset of diabetic nephropathy [19,21,22,32,33,[43][44][45]. IGFBPs bind IGF peptides with high affinities and can modulate IGF localization to cellular targets and IGF receptor activation [46,47].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line

Davis

Rodgers

Kelley

2008

Endocr

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In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IG-FBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.

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“…IGFBPs have also been implicated in the development of nephropathy in human and rodent models (3,4,(23)(24)(25)(26)30,32,33). Flyvbjerg et al (33) and Landau et al (31) reported that the growth hormone, the principle biological regulator of IGF-I secretion, enhances diabetes-related renal IGFBP-1 upregulation at the mRNA and protein levels and exacerbates diabetic renal hypertrophy in STZ rats.…”

Section: Igfbp-1 Snps and Diabetic Nephropathymentioning

confidence: 99%

“…Renal hypertrophy is an earlyonset feature of experimental diabetic nephropathy and is correlated with an increase in IGF-I and a transient spike in IGFBP-1. However, cortical regulation of the IGF effect is mediated by IGFBPs (3,4,[23][24][25][26][27]. Feldmann et al (27) reported lower free IGF-I levels but an elevated total IGF-1 level, strongly suggesting a modulatory role for IGFBPs in this process.…”

mentioning

confidence: 99%

“…IGF-I and -II possess significant structural homology with insulin and consequently exert acute metabolic effects on carbohydrate and protein metabolism in addition to their potent mitogenic effects. IGF-I and -II have been linked to the pathogenesis of diabetic nephropathy, retinopathy, cardiovascular disease, deteriorating glucose tolerance, and weight gain (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

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Polymorphisms in igf-Binding Protein 1 Are Associated With Impaired Renal Function in Type 2 Diabetes

et al. 2005

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The dysregulation of the IGF system has been implicated in the pathogenesis of obesity, diabetes, and diabetes complications such as nephropathy, but little is known about the genomics of the IGF system in health and disease. We genotyped 13 single nucleotide polymorphisms (SNPs) in IGFBP1 gene in 732 representative type 2 diabetic patients from the Salford Diabetes Register. Of the 13 SNPs, 8 were polymorphic and 7 of those had minor allele frequencies >0.1, one of which was in the gene promoter and one of which was nonsynonymous in exon 4. The minor alleles of these SNPs and two others were associated with a reduced prevalence of diabetic nephropathy. Haplotype analysis revealed that 97% of the genetic variation for IGFBP1 in the population sample could be accounted for using two of the "reno-protective" SNPs, with other SNPs adding little extra information. One of these two SNPs was the nonsynonymous mutation in exon 4, lying close to the integrinbinding RGD motif, which is thought to affect tissue delivery of IGF-I by IGF-binding protein 1 (IGFBP-1), possibly suggesting a "reno-protective" effect via altered IGFBP-1 binding. In conclusion, we have described the first genomic markers to be associated with diabetic microvascular complications within the human IGFBP1 gene. Diabetes 54: [3547][3548][3549][3550][3551][3552][3553] 2005 T he IGF system is increasingly implicated in the development of type 2 diabetes and its complications. IGF-I and -II possess significant structural homology with insulin and consequently exert acute metabolic effects on carbohydrate and protein metabolism in addition to their potent mitogenic effects. IGF-I and -II have been linked to the pathogenesis of diabetic nephropathy, retinopathy, cardiovascular disease, deteriorating glucose tolerance, and weight gain (1-13).Unlike insulin, the effects of IGFs are modulated by specific IGF-binding proteins (IGFBPs), six of which have been well characterized (14,15). Of the six IGFBPs, IGFBP-1 is considered to be the principal acute regulator of IGF-I activity (16), forming a link between dietary ingestion, glucose metabolism, and the IGF axis. IGFBP-1 synthesis is limited to the liver, decidua, and kidney and is acutely inhibited by insulin via binding of hepatocyte nuclear factor-3␤ (HNF-3␤) to the insulin-response elements of the gene promoter. Conversely, increased IGFBP-1 production is primarily associated with cAMP and glucocorticoids acting via specific promoter elements, although increased synthesis is also associated with hyperglycemia (via upstream stimulatory factor 1 [USF-1]) and hypoxia (via the hypoxia-inducible transcription factor 1␣ [HIF-1␣] and nitric oxide) (17-22). Thus, IGFBP-1 is acutely metabolically regulated, unlike other IGFBPs (16). Rodent models and clinical observations have underlined the potential importance of IGFBP-1 dysregulation in the etiology of diabetic complications such as macrovascular disease and microvascular conditions such as nephropathy and retinopathy. Renal hypertrophy is an earlyonset feat...

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Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats

Cited by 27 publications

References 40 publications

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹

Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line

Polymorphisms in igf-Binding Protein 1 Are Associated With Impaired Renal Function in Type 2 Diabetes

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Preferential expression of insulin-like growth factor binding proteins- 1, -3, and -5 during early diabetic renal hypertrophy in rats

Cited by 27 publications

References 40 publications

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model1

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model1

Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line

Polymorphisms in igf-Binding Protein 1 Are Associated With Impaired Renal Function in Type 2 Diabetes

Contact Info

Product

Resources

About

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹

Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model¹