IGFBP7
Insulin-like growth factor-binding protein 7 precursor (IBP-7) (IGF-binding protein 7) (IGFBP-7) (IGFBP-rP1) (MAC25 protein) (PGI2-stimulating factor) (Prostacyclin-stimulating factor) (Tumor-derived adhesion factor) (TAF) [MAC25] [PSF]
Publications[править]
The induced pluripotent stem cell (iPSC) is a promising cell source for tissue regeneration. However, the therapeutic value of iPSC technology is limited due to the complexity of induction protocols and potential risks of teratoma formation. A trans-differentiation approach employing natural factors may allow better control over reprogramming and improved safety. We report here a novel approach to drive trans-differentiation of human fibroblasts into functional osteoblasts using insulin-like growth factor binding protein 7 (IGFBP7). We initially determined that media conditioned by human osteoblasts can induce reprogramming of human fibroblasts to functional osteoblasts. Proteomic analysis identified IGFBP7 as being significantly elevated in media conditioned with osteoblasts compared with those with fibroblasts. Recombinant IGFBP7 induced a phenotypic switch from fibroblasts to osteoblasts. The switch was associated with senescence and dependent on autocrine IL-6 signaling. Our study supports a novel strategy for regenerating bone by using IGFBP7 to trans-differentiate fibroblasts to osteoblasts.
Keywords
- IGFBP7
- IL-6
- human fibroblast
- osteoblast
- reprogramming
- senescence
Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through [i]day 3[/i], when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at [i]day 1[/i] in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on [i]day 3[/i], suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.
MeSH Terms
- Acute Kidney Injury
- Age Factors
- Aging
- Animals
- Autophagy
- Cell Proliferation
- Cisplatin
- Creatinine
- Cytokines
- Disease Models, Animal
- Female
- Heme Oxygenase-1
- Hepatitis A Virus Cellular Receptor 1
- Insulin-Like Growth Factor Binding Proteins
- Kidney
- Lipocalin-2
- Male
- Membrane Proteins
- Methionine Adenosyltransferase
- Mice, Inbred C57BL
- Sex Factors
- Signal Transduction
- Time Factors
Keywords
- Cisplatin
- acute kidney injury
- aging
- autophagy
- cytokines
- female
- heme oxygenase-1
- kidney injury markers
- sex differences
The IGFBP7 gene encodes insulin-like growth factor protein 7. IGFPB7 is involved in diverse biological functions including cell growth regulation, senescence and apoptosis, and also acts as a tumor suppressor in multiple cancers. The IGFBP7 mRNA is subject to A-to-I RNA editing mediated by adenosine deaminases acting on RNA 1 and 2 (ADAR1 and ADAR2). In the current study we have examined molecular characteristics of the porcine IGFBP7 gene, and determined the mRNA editing in different tissues. The A-to-I RNA editing of human IGFBP7 in positions Arg78 and Lys95 was shown to be conserved in the porcine homologue. In addition, a novel editing site was discovered in position Lys97 in the porcine IGFBP7 transcript. A differential editing was demonstrated at the three positions in the IGFBP7 transcript with very high degrees of editing in frontal cortex, cerebellum and lung. Interestingly, the degree of editing increased during aging in porcine frontal cortex and cerebellum. The IGFBP7 gene was mapped to pig chromosome 8. The porcine IGFBP7 gene was found to be ubiquitously expressed in examined organs and tissues. The methylation status of the IGFBP gene was examined in brain and liver by bisulfate sequencing and a high degree of methylation was found in the two tissues, 52% and 54%, respectively.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Arginine
- Binding Sites
- Brain
- Brain Mapping
- Cerebellum
- Chromosome Mapping
- Female
- Frontal Lobe
- Gene Expression Profiling
- Gene Expression Regulation
- Humans
- Insulin-Like Growth Factor Binding Proteins
- Lung
- Lysine
- Methylation
- Mice
- RNA Editing
- RNA, Messenger
- RNA-Binding Proteins
- Sulfates
- Swine
Keywords
- Brain
- IGFBP7
- RNA editing
Hepatocellular carcinoma (HCC) is a vicious and highly vascular cancer with a dismal prognosis. It is a life-threatening illness worldwide that ranks fifth in terms of cancer prevalence and third in cancer deaths. Most patients are diagnosed at an advanced stage by which time conventional therapies are no longer effective. Targeted molecular therapies, such as the multikinase inhibitor sorafenib, provide a modest increase in survival for advanced HCC patients and display significant toxicity. Thus, there is an immense need to identify novel regulators of HCC that might be targeted effectively. The insulin-like growth factor (IGF) axis is commonly abnormal in HCC. Upon activation, the IGF axis controls metabolism, tissue homeostasis, and survival. Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein of a family of low-affinity IGF-binding proteins termed "IGFBP-related proteins" that have been identified as a potential tumor suppressor in HCC. IGFBP7 has been implicated in regulating cellular proliferation, senescence, and angiogenesis. In this review, we provide a comprehensive discussion of the role of IGFBP7 in HCC and the potential use of IGFBP7 as a novel biomarker for drug resistance and as an effective therapeutic strategy.
Keywords
- HCC
- IGFBP7
- angiogenesis
- apoptosis
- gene therapy
- senescence