Редактирование: BMP6

Bone morphogenetic protein 6 precursor (BMP-6) (VG-1-related protein) (VG-1-R) (VGR-1) [VGR]

==Publications==

{{medline-entry
|title=[[GREM1]] inhibits osteogenic differentiation, senescence and BMP transcription of adipose-derived stem cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32151168
|abstract=: Adipose-derived stem cells (ADSCs) are ideal for cell-based therapies to support bone regeneration. It is vital to understand the critical genes and molecular mechanisms involved in the functional regulation of ADSCs for enhancing bone regeneration. In the present study, we investigated the Gremlin 1 ([[GREM1]]) effect on ADSCs osteogenic differentiation and senescence. : The [i]in vitro[/i] ADSCs osteogenic differentiation potential was evaluated by determining alkaline phosphatase (ALP) activity, mineralization ability, and the expression of osteogenic markers. Cell senescence is determined by SA-β-gal staining, telomerase assay, and the expression of aging markers. : [[GREM1]] overexpression in ADSCs reduced ALP activity and mineralization, inhibited the expression of osteogenic related genes [i]OCN, OPN, [[DSPP]], [[DMP1]][/i], and [i]BSP[/i], and key transcription factors, [i]RUNX2[/i] and [i]OSX[/i]. [[GREM1]] knockdown in ADSCs enhanced ALP activity and mineralization, promoted the expression of [i]OCN, OPN, [[DSPP]], [[DMP1]], BSP, RUNX2[/i], and [i]OSX[/i]. [[GREM1]] overexpression in ADSCs reduced the percent SA-β-Gal positive cells, [i]P16[/i] and [i]P53[/i] expressions, and increased telomerase activity. [[GREM1]] knockdown in ADSCs increased the percentage of SA-β-Gal positive cells, [i]P16[/i] and [i]P53[/i] expressions, and reduced telomerase activity. Furthermore, [[GREM1]] reduced the mRNA expression levels of [[BMP2]], [[BMP6]], and [[BMP7]]. : In summary, our findings suggested that [[GREM1]] inhibited ADSCs senescence and osteogenic differentiation and antagonized BMP transcription.

|keywords=* BMP
* GREM1
* adipose-derived stem cells (ADSCs)
* osteogenic differentiation
* senescence
|full-text-url=https://sci-hub.do/10.1080/03008207.2020.1736054
}}
{{medline-entry
|title=Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30352848
|abstract=Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer's disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in [[BMP6]] protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that [[BMP6]] severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain's natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.
|mesh-terms=* Adult Stem Cells
* Aging
* Alzheimer Disease
* Animals
* Astrocytes
* Bone Morphogenetic Protein 6
* Carrier Proteins
* Cell Differentiation
* Disease Models, Animal
* Hippocampus
* Humans
* Injections, Intraventricular
* Male
* Mice
* Mice, Transgenic
* Neural Stem Cells
* Neurogenesis
* Neurons
* Neuroprotective Agents
* Signal Transduction
|keywords=* Alzheimer’s disease
* BMP signaling
* adult neurogenesis
* aging
* neural stem cells
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233090
}}
{{medline-entry
|title=Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28583802
|abstract=Cyp1b1 deletion and gestational vitamin A deficiency (GVAD) redirect adult liver gene expression. A matched sufficient pre- and post-natal diet, which has high carbohydrate and normal iron content (LF12), increased inflammatory gene expression markers in adult livers that were suppressed by GVAD and Cyp1b1 deletion. At birth on the LF12 diet, Cyp1b1 deletion and GVAD each suppress liver expression of the iron suppressor, hepcidin (Hepc), while increasing stellate cell activation markers and suppressing post-natal increases in lipogenesis. Hepc was less suppressed in Cyp1b1-/- pups with a standard breeder diet, but was restored by iron supplementation of the LF12 diet. The LF12 diet delivered low post-natal iron and attenuated Hepc. Hepc decreases in Cyp1b1-/- and GVAD mice resulted in stellate activation and lipogenesis suppression. Endothelial [[BMP6]], a Hepc stimulant, is a potential coordinator and Cyp1b1 target. These neonatal changes in Cyp1b1-/- mice link to diminished adult obesity and liver inflammation.
|mesh-terms=* Adiposity
* Aging
* Animals
* Animals, Newborn
* Biomarkers
* Cytochrome P-450 CYP1B1
* Diet
* Erythropoiesis
* Esters
* Female
* Gene Deletion
* Gene Expression Regulation, Developmental
* Hepatic Stellate Cells
* Hepatocytes
* Hepcidins
* Insulin-Like Growth Factor II
* Iron
* Lipogenesis
* Liver
* Male
* Mice, Inbred C57BL
* Obesity
* Organ Size
* Pregnancy
* Vitamin A
* Vitamin A Deficiency
* Weaning
* alpha-Fetoproteins
|keywords=* Cytochrome P450 1b1
* Hepcidin
* Lipogenesis
* Vitamin A
* Vitamin A deficiency
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985816
}}
{{medline-entry
|title=Age-dependent shifts in renal response to injury relate to altered [[BMP6]]/CTGF expression and signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27558559
|abstract=Age is associated with an increased prevalence of chronic kidney disease (CKD), which, through progressive tissue damage and fibrosis, ultimately leads to loss of kidney function. Although much effort is put into studying CKD development experimentally, age has rarely been taken into account. Therefore, we investigated the effect of age on the development of renal tissue damage and fibrosis in a mouse model of obstructive nephropathy (i.e., unilateral ureter obstruction; UUO). We observed that after 14 days, obstructed kidneys of old mice had more tubulointerstitial atrophic damage but less fibrosis than those of young mice. This was associated with reduced connective tissue growth factor (CTGF), and higher bone morphogenetic protein 6 ([[BMP6]]) expression and pSMAD1/5/8 signaling, while transforming growth factor-β expression and transcriptional activity were no different in obstructed kidneys of old and young mice. In vitro, CTGF bound to and inhibited [[BMP6]] activity. In summary, our data suggest that in obstructive nephropathy atrophy increases and fibrosis decreases with age and that this relates to increased BMP signaling, most likely due to higher [[BMP6]] and lower CTGF expression.
|mesh-terms=* Age Factors
* Animals
* Bone Morphogenetic Protein 6
* Connective Tissue Growth Factor
* Disease Models, Animal
* Fibrosis
* Kidney
* Mice
* Phosphorylation
* Renal Insufficiency, Chronic
* Signal Transduction
* Smad Proteins
* Transforming Growth Factor beta
* Ureteral Obstruction
|keywords=* BMP
* CKD
* CTGF
* UUO
* aging
|full-text-url=https://sci-hub.do/10.1152/ajprenal.00324.2016
}}
{{medline-entry
|title=Iron-mediated retinal degeneration in haemojuvelin-knockout mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21943374
|abstract=Haemochromatosis is a genetic disorder of iron overload resulting from loss-of-function mutations in genes coding for the iron-regulatory proteins [[HFE]] (human leucocyte antigen-like protein involved in iron homoeostasis), transferrin receptor 2, ferroportin, hepcidin and [[HJV]] (haemojuvelin). Recent studies have established the expression of all of the five genes in the retina, indicating their importance in retinal iron homoeostasis. Previously, we demonstrated that [[HJV]] is expressed in [[RPE]] (retinal pigment epithelium), the outer and inner nuclear layers and the ganglion cell layer. In the present paper, we report on the consequences of Hjv deletion on the retina in mice. Hjv-/- mice at ≥18 months of age had increased iron accumulation in the retina with marked morphological damage compared with age-matched controls; these changes were not found in younger mice. The retinal phenotype in Hjv-/- mice included hyperplasia of [[RPE]]. We isolated [[RPE]] cells from wild-type and Hjv-/- mice and examined their growth patterns. Hjv-/- [[RPE]] cells were less senescent and exhibited a hyperproliferative phenotype. Hjv-/- [[RPE]] cells also showed up-regulation of Slc7a11 (solute carrier family 7 member 11 gene), which encodes the 'transporter proper' subunit xCT in the heterodimeric amino acid transporter xCT/4F2hc (cystine/glutamate exchanger). [[BMP6]] (bone morphogenetic protein 6) could not induce hepcidin expression in Hjv-/- [[RPE]] cells, confirming that retinal cells require [[HJV]] for induction of hepcidin via [[BMP6]] signalling. [[HJV]] is a glycosylphosphatidylinositol-anchored protein, and the membrane-associated [[HJV]] is necessary for [[BMP6]]-mediated activation of hepcidin promoter in [[RPE]] cells. Taken together, these results confirm the biological importance of [[HJV]] in the regulation of iron homoeostasis in the retina and in [[RPE]].
|mesh-terms=* Aging
* Amino Acid Transport System y 
* Animals
* Antimicrobial Cationic Peptides
* Bone Morphogenetic Protein 6
* GPI-Linked Proteins
* Hemochromatosis Protein
* Hepcidins
* Histocompatibility Antigens Class I
* Iron
* Iron-Regulatory Proteins
* Male
* Membrane Proteins
* Mice
* Mice, Knockout
* Retina
* Retinal Degeneration
* Retinal Pigment Epithelium

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710445
}}