Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although granulocyte colony-stimulating factor (G-CSF) was originally isolated as an activity for the growth and differentiation of cells in granulocytic lineage, it has been gradually accepted that G-CSF may have a function on a wide variety of cells besides granulocytes. To elucidate the function of G-CSF on bone cells in vivo, we examined the bone tissue of transgenic mice that overexpress G-CSF. Transgenic mice express human G-CSF at an elevated level (1041 +/- 242 pg/ml in sera) under the direction of SRalpha promoter. We performed radiographic, routine histologic, and histomorphometric analyses of the bone tissue and serum biochemical assay. Nontransgenic littermates were examined as age-matched, wild-type controls in all experiments. Radiographic analysis revealed cortical thinning accompanied by enlarged bone marrow cavities in both vertebral bodies and long bones. Histologically, a decreased number and thickness of trabecular bones and cortical thinning were observed in lumber vertebrae as well as in femur specimens. The enlarged bone marrow cavities exhibited an increased number of mature neutrophilic granulocytes without apparent changes in other types of cells. The static and dynamic parameters reflecting bone resorption were found to be significantly increased in the transgenic mice. By contrast, no significant differences were detected in the parameters reflecting bone formation. Transgenic mice and littermate controls had similar serum calcium, phosphorous, and alkaline phosphatase levels. However, the serum osteocalcin level was significantly higher in transgenic mice. These findings indicate that G-CSF-expressing transgenic mice developed osteoporosis because of increased osteoclastic activity. Collectively, G-CSF could have a negative influence on bone homeostasis in vivo.
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PMID:Overexpression of the granulocyte colony-stimulating factor gene leads to osteoporosis in mice. 860 92

We hypothesized that therapy, composed of antiapoptotic soluble Fas (sFas) gene transfer, combined with administration of the cardioprotective cytokine granulocyte colony-stimulating factor (G-CSF), would markedly mitigate cardiac remodeling and dysfunction following myocardial infarction (MI). On the 3rd day after MI induced by ligating the left coronary artery in mice, four different treatments were initiated: saline injection (Group C, n = 26); G-CSF administration (Group G, n = 27); adenoviral transfer of sFas gene (Group F, n = 26); and the latter two together (Group G+F, n = 26). Four weeks post-MI, Group G+F showed better survival than Group C (96 vs. 65%, P < 0.05) and the best cardiac function among the four groups. In Group G, the infarct scar was smaller and less fibrotic, whereas in Group F the scar was thicker, without a reduction in area, and contained abundant myofibroblasts and vascular cells; Group G+F showed both phenotypes. G-CSF exerted a beneficial effect on infarct tissue dynamics through antifibrotic and proliferative effects on granulation tissue; however, it also exerts an adverse proapoptotic effect that leads to thinning of the infarct scar. sFas appeared to offset the latter drawback. In vitro study using cultured myofibroblasts derived from the infarct tissue revealed that G-CSF increased proliferating activity of those cells accompanying activation of Akt and signal transducer and activator of transcription 3, while accelerating Fas-mediated apoptosis with increasing Bax-to-Bcl-2 ratio. The results suggest that combined use of G-CSF administration and sFas gene therapy is a potentially powerful tool against post-MI heart failure.
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PMID:Combined therapy with cardioprotective cytokine administration and antiapoptotic gene transfer in postinfarction heart failure. 1920 3

The purpose of the present study was to investigate whether systemically administered granulocyte colony-stimulating factor (G-CSF) can protect against acute ischemic reperfusion injury. Two groups of anesthetized adult male Lewis rats (n = 8 per group) were subjected to an acute (45 min) episode of retinal ischemic injury followed by subcutaneous administration of vehicle (5% dextrose) or G-CSF (0.1 mg/kg/day) once per day x 5 days. Prior to and one week following ischemic insult, retinal function was measured by scotopic electroretinography (ERG). Retinas were harvested and morphologically analyzed one week after ischemic insult. ERG a- and b-wave amplitudes were significantly reduced following ischemic reperfusion injury. G-CSF treatment attenuated ischemic-induced loss of retinal function. In control vehicle-treated rats, ischemic reperfusion injury elicited marked and selective thinning of inner retinal layers while only minimally affecting outer retinal layers. Therapeutically administered G-CSF minimized ischemic-mediated thinning of whole retina and inner retinal layers. G-CSF may be of therapeutic interest for the management of retinal ischemic disorders.
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PMID:Granulocyte colony-stimulating factor facilitates recovery of retinal function following retinal ischemic injury. 2039 6

Proliferative and secretory changes at the endometrial lining are the result of a complex intrauterine environment where sex steroid hormones and different local factors play an important role for endometrial thickening. Optimal endometrial thickness reflects an adequate maturation which is a key factor for embryo implantation. Here, we present a case of a woman with polycystic ovary who was treated using in vitro maturation (IVM) techniques. In addition, this patient showed a dyssynchrony between the endometrial phase characterised by endometrial thinning and the embryo development which had a negative impact for embryo implantation. A protocol using uterine perfusion of granulocyte colony-stimulating factor (G-CSF) was performed as an alternative treatment for the unresponsive endometrium. We found that uterine infusion of G-CSF quickly increased endometrial thickness resulting in a successful pregnancy and healthy born baby. These results suggest that G-CSF is a factor that participates during endometrial remodelling enhancing the synchronisation between uterine environment and embryo development.
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PMID:Granulocyte colony-stimulating factor (G-CSF): a mediator in endometrial receptivity for a patient with polycystic ovary (PCO) undergoing in vitro maturation (IVM). 2360 19

Treatment with granulocyte colony-stimulating factor (G-CSF) reportedly mitigates postinfarction cardiac remodeling and dysfunction. We herein examined the effects of G-CSF knockout (G-CSF-KO) on the postinfarction remodeling process in the hearts of mice. Unexpectedly, the acute infarct size 24 hours after ligation was similar in the two groups. At the chronic stage (4 weeks later), there was no difference in the left ventricular dimension, left ventricular function, or histological findings, including vascular density, between the two groups. In addition, expression of vascular endothelial growth factor (VEGF) was markedly up-regulated in hearts from G-CSF-KO mice, compared with wild-type mice. Microarray failed in detecting up-regulation of VEGF mRNA, whereas G-CSF administration significantly decreased myocardial VEGF expression in mice, indicating that G-CSF post-transcriptionally down-regulates VEGF expression. When G-CSF-KO mice were treated with an anti-VEGF antibody (bevacizumab), cardiac remodeling was significantly aggravated, with thinning of the infarct wall and reduction of the cellular component, including blood vessels. In the granulation tissue of bevacizumab-treated hearts 4 days after infarction, vascular development was scarce, with reduced cell proliferation and increased apoptosis, which likely contributed to the infarct wall thinning and the resultant increase in wall stress and cardiac remodeling at the chronic stage. In conclusion, overexpression of VEGF may compensate for the G-CSF deficit through preservation of cellular components, including blood vessels, in the postinfarction heart.
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PMID:Postinfarction Cardiac Remodeling Proceeds Normally in Granulocyte Colony-Stimulating Factor Knockout Mice. 2597 46