Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Aged ; Animals ; Bone Density ; Diabetes Mellitus, Experimental/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/etiology* ; Rats ; Receptor, IGF Type 1/physiology* ; Signal Transduction ; Streptozocin ; beta Catenin/physiology*

OBJECTIVETo study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts.

METHODSRat lung fibroblasts and rat alveolar macrophages were cultured. A transdifferentiation model of primary rat lung fibroblasts was induced by free silica. Levels of α-SMA protein, IGF-IIR protein and mRNA were measured by immunocytochemistry, Western blot and RT-PCR, respectively. Lung fibroblasts were treated with Wortmannin.

RESULTSThe expression levels of α-SMA and IGF-IIR increased with the increasing free silica concentration and decreased after Wortmannin was used.

CONCLUSIONThe IGF-IIR plays an important role in free silica-induced transdifferentiation of primary rat lung fibroblasts.

Animals ; Base Sequence ; Cell Differentiation ; physiology ; Cells, Cultured ; DNA Primers ; Fibroblasts ; drug effects ; Lung ; cytology ; drug effects ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, IGF Type 2 ; genetics ; physiology ; Silicon Dioxide ; pharmacology

OBJECTIVETo investigate the effect of Yangjing Zhongyu Decoction (YJZYD) on expression of insulin-like growth factor II (IGF-II) and its receptor II (IGF-II R) in endometrium of women with unexplained infertility, and the relationship of which with the receptibility of endometrium to ovum implantation.

METHODSReverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect quantitatively the expression of IGF-II and IGF-II R in 22 women with unexplained infertility before and after YJZYD treatment during mid-luteal phase.

RESULTSThe levels of IGF-II and IGF-II R before treatment were 0.794 +/- 0.453 and 0.725 +/- 0.354 (in grey level, the same below) respectively, which were significantly increased in the same phase after treatment, reaching 1.202 +/- 0.551 and 1.045 +/- 0.581 respectively (P < 0.01 and P < 0.05). Correlation analysis showed the level of IGF-II mRNA was positively correlated with the level of IGF-II mRNA either before or after treatment.

CONCLUSIONYJZYD could enhance the expression of IGF-II and IGF-II R in the endometrium during mid-luteal phase, promote the differentiation of endometrium and increase its reception to ovum implantation.

Adult ; Embryo Implantation ; drug effects ; Endometrium ; metabolism ; Female ; Humans ; Infertility, Female ; drug therapy ; metabolism ; Insulin-Like Growth Factor II ; biosynthesis ; genetics ; Luteal Phase ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, IGF Type 2 ; biosynthesis ; genetics

OBJECTIVETo determine the microsatellite instability in gastric carcinomas, examine the frameshift mutations of transforming growth factor-beta type II receptor (TGFbetaRII), insulin growth factor II receptor (IGFIIR), bcl-2 associated X protein (BAX) and E2F4, and investigate whether or how alterations of the TGFbetaRII, IGFIIR, BAX and E2F4 gene are associated with MSI in gastric cancer.

METHODSFormalin-fixed, paraffin-embedded gastrectomy specimens and matching normal tissues of 65 cases of gastric carcinomas were retrieved from shanghai Ruijin Hospital and Shanghai East Hospital. DNA was extracted from tissue sections using phenol chloral isoamyl alcohol. Sections with no more than 50% of tumor cell areas were isolated by microdissection. DNA was amplified by PCR-based single strand conformation polymorphism (SSCP) for microsatellite analysis and was sequenced directly. Frameshift mutations in the coding regions, repetitive mononucleotide tracts of (A)10 for TGFbetaRII, (G)8 for IGFIIR, (G)8 for BAX, and trinucleotide repeats of (AGC)13 for transcription factors E2F4 were detected using PCR. Tumors were classified as being microsatellite stable (MSS) or having a low frequency of MSI (MSI-L, one of markers different in the tumor) or a high frequency of MSI (MSI-H, two or more of markers different).

RESULTSEleven cases (18.0%) showed MSI-L, 12 (19.7%) showed MSI-H and 38 (62.3%) cases showed MSS. The mutation rates of TGFbetaRII, IGFIIR, BAX and E2F4 gene were 19.7%, 4.9%, 6.6% and 16.4% respectively. Among the 12 MSI-H gastric cancers, there were 10 TGFbetaRII mutations, 3 IGFIIR mutations, 4 BAX mutations and 10 E2F4 gene mutations. The alterations in the repeats of the related genes presented polymorphisms. Associations of MSI-H status and mutations of the 4 genes were highly significant (P < 0.01, respectively). No repeat tracts mutations in TGFbetaRII, IGFIIR, BAX and E2F4 gene were found in MSS tumors.

CONCLUSIONSThe repeat coding regions within TGFbetaRII, IGFIIR, BAX and E2F4 gene are the targets of microsatellite instability. Frameshift mutations of the 4 genes play an important role in the development and progression of gastric cancers with microsatellite instability.

Adult ; Aged ; Aged, 80 and over ; China ; E2F4 Transcription Factor ; genetics ; Female ; Frameshift Mutation ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases ; Receptor, IGF Type 2 ; genetics ; Receptors, Transforming Growth Factor beta ; genetics ; Stomach Neoplasms ; genetics ; bcl-2-Associated X Protein ; genetics