Progress in growth factor research最新文献

{"title":"Cellular localization and hormonal regulation of biosynthesis of insulin-like growth factor binding proteins and of the acid-labile subunit within rat liver","authors":"Jens-Gerd Scharf ,&nbsp;Giuliano Ramadori ,&nbsp;Thomas Braulke ,&nbsp;Heinz Hartmann","doi":"10.1016/0955-2235(95)00031-3","DOIUrl":"10.1016/0955-2235(95)00031-3","url":null,"abstract":"<div><p>In the circulation, most of the IGFs are bound to a high molecular weight binding protein complex of 150 kDa that consists of IGF-I (or IGF-II), IGFBP-3 and the acid-labile subunit (ALS). Within rat liver, individual components of the 150 kDa complex are synthesized in different cellular compartments: ALS expression in localized in hepatocytes, but not in non-parenchymal cells. IGFBP-3 mRNA, however, is exclusively expressed in non-parenchymal and among them in endothelial and Kupffer cells.</p><p>Co-cultures of hepatocytes and Kupffer cells were used as a model to study the hormonal regulation of biosynthesis of the components of the 150 kDa complex. Although expressed in different liver cell populations IGFBP-3 and ALS were regulated synergistically. Insulin stimulated both the expression of ALS and IGFBP-3 in co-cultures in a dose-dependent manner, while expression of IGFBP-1 was decreased. Regulation of IGFBP-3 synthesis of Kupffer cells required a mediator that is secreted by hepatocytes, since IGFBP-3 expression in cultures of pure Kupffer cells did not respond to the stimulating effect of insulin.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 175-180"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00031-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factors (IGF) and IGF binding proteins in children with chronic renal failure","authors":"Burkhard Tönshoff,&nbsp;Werner F. Blum ,&nbsp;Otto Mehls","doi":"10.1016/0955-2235(96)00003-8","DOIUrl":"10.1016/0955-2235(96)00003-8","url":null,"abstract":"<div><p>The pathomechanism of growth retardation and catabolism in children with chronic renal failure (CRF) is multifactorial. Recent evidence indicates that in particular disturbances of the somatotropic hormone axis play an important pathogenic role. In preterminal CRF serum insulin-like growth factor (IGF)-I and IGF-II levels are normal, while in end-stage renal disease (ESRD), IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels appear as inadequately low. Indeed, there is both clinical and experimental evidence for a decreased hepatic IGF-I production rate in CRF. This hepatic insensitivity to the action of GH is partially owing to a reduced GH receptor expression. The action and metabolism of IGFs are modulated by specific high-affinity IGF binding proteins (IGFBPs), which bind ∼99% of circulating IGF. IGFBP-1, IGFBP-2, and low molecular weight IGFBP-3 fragments are increased in CRF serum in relation to the degree of renal dysfunction. Both decreased renal filtration, in particular of low molecular weight IGFBP-3 fragments, and increased hepatic production of IGFBP-1 and -2 contribute to high IGFBP serum levels. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action on target tissues by competition with the type 1 IGF receptor for IGF binding.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 481-491"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(96)00003-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human insulin-like growth factor binding protein-1 (hiGFBP-1) transgenic mice: Insights into hIGFBP-1 regulation and actions","authors":"A.J. D'Ercole,&nbsp;P. Ye,&nbsp;Z. Dai","doi":"10.1016/0955-2235(95)00010-0","DOIUrl":"10.1016/0955-2235(95)00010-0","url":null,"abstract":"<div><p>Three hemizygous transgenic (Tg) mouse lines were generated with a fusion gene composed of the mouse metallothionein promoter (mMT-1) and a full length human insulin-like growth factor binding protein-1 (hIGFBP-1) cDNA that was truncated in its 3′ untranslated (3′UT) region. The transgene was ectopically expressed in the brain of each line and resulted in postnatal brain-growth retardation that was manifested by 2 weeks of age. Despite the expression of the transgene in multiple other tissues and high serum hIGFBP-1 concentrations in two of the three lines, studies designed to detect alterations in somatic growth, in reproduction and in glucose metabolism revealed few other abnormalities. Unexpectedly, however, we found that the regulation of the transgene shared characteristics with that of the native gene, despite the fact that it lacked the endogenous gene's 5′ regulatory region, as well as most of its 3′ UT region. Our studies suggest that factors controlling mRNA stability are important to regulation of both the native and transgene, and that an AU-rich element 17 base pairs (bp) from the end of coding sequence is responsible for the instability of the transgene and in part for instability of the endogenous gene.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 417-423"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00010-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of the rat acid-labile subunit gene","authors":"Patric J.D. Delhanty,&nbsp;Robert C. Baxter","doi":"10.1016/0955-2235(95)00011-9","DOIUrl":"10.1016/0955-2235(95)00011-9","url":null,"abstract":"<div><p>The acid-labile subunit (ALS) of the ternary insulin-like growth factor binding protein (IGFBP) complex has a central role in regulating the bioavailability of circulating IGF. We have shown that gene expression of ALS <em>in vivo</em> and <em>in vitro</em> is regulated by a variety of factors, including growth hormone (GH). Our aim was to isolate and characterise the ALS gene as a step in defining the mechanism of its regulation. Southern analysis of rat genomic DNA suggests that the ALS gene exists as a single copy in the rat genome. In order to isolate this gene we screened 5×10⁵ clones and selected fragments of two genomic clones were sequenced. Comparison of this sequence with the cDNA identified two exons and a single ∼1.1 kb intron. Primer extension experiments suggest two major transcription initiation sites at −539 and −396 nts relative to the translational initiation codon, although there are no consensus TATA-boxes in this region. Analysis of 2.3 kb of 5′ flanking sequence identified two LF-A1 sites which may confer the liver-specific expression of the ALS gene. In addition, there are several elements that may be involved in regulation by growth hormone and cytokines.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 141-149"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00011-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice","authors":"Thomas Braulke ,&nbsp;Max Claussen ,&nbsp;Paul Saftig ,&nbsp;Martin Wendland ,&nbsp;Klaus Neifer ,&nbsp;Bernhard Schmidt ,&nbsp;Jürgen Zapf ,&nbsp;Kurt bon Figura ,&nbsp;Christoph Peters","doi":"10.1016/0955-2235(95)00005-4","DOIUrl":"10.1016/0955-2235(95)00005-4","url":null,"abstract":"<div><p>Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP <em>in vivo</em>, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 265-271"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00005-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19785519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines regulate IGF binding proteins in the CNS","authors":"Teresa L. Wood,&nbsp;Steven L. O'Donnell,&nbsp;Steven W. Levison","doi":"10.1016/0955-2235(95)00035-6","DOIUrl":"10.1016/0955-2235(95)00035-6","url":null,"abstract":"<div><p>Growth factor induction is a major component of the response to central nervous system trauma. The insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) are among the molecules induced by injury that have demonstrated neuroprotective actions. Induction of IGFBPs 2, 3, 4 and 5 have been documented following injury and are hypothesized to function in transport or localization of the IGFs to injured cells. It is unclear what factors lead to induction of these molecules following trauma, however, several cytokines including ciliary neurotrophic factor (CNTF) and interleukin-1β (IL-1β) have been described as major injury signals and can induce aspects of reactive gliosis. To establish whether these cytokines also are responsible for inducing the IGFBPs following CNS injury, we injected CNTF or IL-1β intracerebrally into the neocortex of adult rats and measured changes in mRNA expression for the IGFBPs. IGFBP-2 mRNA showed a dramatic increase by 24–48 h following either CNTF or IL-1β injection as compared with the contralateral side injected with heat-inactivated cytokine. Neither CNTF nor IL-1β caused alterations in BP3 or BP5. Levels of BP4 and BP6 mRNAs also were unchanged following CNTF injection. These results suggest that IGFBP2 is uniquely regulated among the IGFBPs in the CNS and is induced by cytokines that signal CNS injury.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 181-187"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00035-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19785565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formation of 150-kDa binary complexes on insulin-like growth factor binding protein-3 and the acid-labile subunit in vitro and in vivo","authors":"C. Young Lee,&nbsp;Matthew M. Rechler","doi":"10.1016/0955-2235(95)00014-3","DOIUrl":"10.1016/0955-2235(95)00014-3","url":null,"abstract":"<div><p>Adult rat serum contains two types of 150-kDa IGFBP complexes: ternary complexes containing bound IGF-I, intact IGFBP-3 and the acid-labile subunit (ALS), and binary complexes that contain ALS and proteolytically-nicked IGFBP-3 but which lack bound IGF. We present evidence that the binary complexes containing proteolytically-nicked IGFBP-3 can be formed in two ways: by direct association of IGFBP-3 with ALS in the absence of IGF, and by proteolysis of IGFBP-3 within 150-kDa ternary complexes, resulting in increased dissociation of IGF-I. The relative contributions of the two mechanisms is unknown. Preliminary results indicate that binary complexes also can form <em>in vivo</em>. Proteolysis of IGFBP-3 in the 150-kDa ternary complex provides a regulatable mechanism by which IGF-I may be mobilized from the circulating reservoir of 150-kDa complexes to the tissues.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 241-251"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00014-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19785572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Components of the IGF system mediate the opposing effects of tamoxifen on endometrial and breast cancer cell growth","authors":"Michael Karas ,&nbsp;Dita Kleinman ,&nbsp;Michael Danilenko ,&nbsp;Charles T. Roberts Jr. ,&nbsp;Derek LeRoith ,&nbsp;Joseph Levy ,&nbsp;Yoav Sharoni","doi":"10.1016/0955-2235(95)00033-X","DOIUrl":"10.1016/0955-2235(95)00033-X","url":null,"abstract":"<div><p>The involvement of the IGF system in the growth regulation of hormone-dependent (e.g. endometrial and breast) cancer cells was studied. We chose two opposing effects of tamoxifen: the paradoxical stimulation of Ishikawa endometrial cancer cells growth and its inhibitory effects on MCF-7 mammary cancer cells. The results clearly confirm our working hypothesis that the IGF system is involved in growth regulation of these cancer cells irrespective of the direction of the drug effect. The following par-ameters of the IGFs system were studied: IGF-I receptors, IGF-I stimulated protein tyrosine phosphorylation, and membrane-associated and secreted IGF-binding proteins (IGFBPs). In Ishikawa cells, tamoxifen, similar to estradiol, increased IGF-I stimulated tyrosine phosphorylation of cellular substrates in accordance with its effect on cell growth. This effect of tamoxifen was inverted in MCF-7 cells. Tamoxifen did not affect the number or affinity of IGF-I receptors in both Ishikawa and MCF-7 cells, however, it caused a three-fold decrease in membrane-associated IGFBPs in the endometrial cells but an increase in these proteins in breast cancer cells. Similar but much less pronounced changes in soluble IGFBPs were observed. Our results indicate that the opposing growth effects of tamoxifen on endometrial and mammary cancer cells are associated with modulation of the IGF system components, mainly with reciprocal changes in membrane-associated IGFBPs.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 513-520"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00033-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in IGFBP-4 and IGFBP-5 levels in human serum and bone: Implications for bone loss with aging","authors":"S. Mohan,&nbsp;J.R. Farley,&nbsp;D.J. Baylink","doi":"10.1016/0955-2235(95)00027-5","DOIUrl":"10.1016/0955-2235(95)00027-5","url":null,"abstract":"<div><p>Osteoporosis develops because of an age-dependent imbalance between the rates of bone formation and bone resorption (i.e. bone formation rate is inadequate compared with bone resorption rate to maintain bone volume). With regard to the mechanism for the deficiency in bone formation, we propose that age-associated changes in the IGF system components contribute to an age-related decrease in the skeletal capacity for osteoblast cell proliferation. As a means of testing this hypothesis, we have measured serum levels of IGFBP-4 and IGFBP-5 since our studies have shown that the mitogenic actions of IGFs in bone cells are modulated by inhibitory IGFBP-4 and stimulatory IGFBP-5. By using newly developed and validated radioimmunoassays for measurement of IGFBP-4 and IGFBP-5, we found that the circulating level of IGFBP-4 increases with age while that of IGFBP-5 declines with age. In subjects from 23–87 years, serum IGFBP-4 concentrations showed a significant positive correlation with serum PTH while serum IGFBP-5 concentrations showed a significant positive correlation with IGF-I. These age-related changes in the serum levels of IGF system components are consistent with our previous findings of age-related decreases in the femoral cortical contents of IGF-I, IGF-II and IGFBP-5. Although the biological implications of the sequestration of IGFs in bone unknown, we have hypothesized that the level of the IGFs in bone is a reflection of their integrated local secretion by osteoblasts. Based on our data, we now propose a model in which (a) underproduction of the stimulatory components and overproduction of an inhibitory component of the IGF system occur as a consequence of aging, and (b) these changes lead to an age-related decrease in the local (autocrine/paracrine) as well as the hormonal (endocrine) actions of the IGFs, which in aggregate could contribute to the decrease in osteoblast proliferation and the deficiency in bone formation. In conclusion, although our findings provide indirect evidence that age associated changes in IGF system components could lead to a deficit in bone formation, further studies are needed to demonstrate a cause and effect relationship between changes in bone cell production of IGF system components and the age-related uncoupling of bone formation from resorption.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 465-473"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00027-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19786568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factor binding protein proteolysis in bone cell models","authors":"Cheryl A. Conover","doi":"10.1016/0955-2235(95)00032-1","DOIUrl":"10.1016/0955-2235(95)00032-1","url":null,"abstract":"<div><p>Insulin-like growth factor binding protein (IGFBP) proteases — their identification, regulation, and biological significance — are currently an area of ardent investigation. This has developed from the very recent realization that IGFBP availability and bioactivity is determined not only by gene expression, but also by the controlled proteolytic processing of the protein in the pertcellular environment. In each case identified so far, the modified IGFBP acts dramatically different from native or recombinant IGFBP in solution. This post-translational modification of IGFBP structure/function could have widespread significance since IGFBPs modulate the diverse growth-promoting activities of the IGFs. In fact, it may be argued that local IGF action is largely controlled by this mechanism. Therefore, knowledge of the form, function, and control of the various IGFBP proteases is likely to have major implications for our understanding of the physiology and pathophysiology of the IGFs.</p></div>","PeriodicalId":77335,"journal":{"name":"Progress in growth factor research","volume":"6 2","pages":"Pages 301-309"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0955-2235(95)00032-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19785523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}