Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotrophic factors appear to be crucial for the survival and potential regeneration of injured neurons. Injury of the peripheral nervous system results in the induction of a number of neurotrophic molecules. Less is known about the response of central nervous tissue to injury. We have examined changes in levels of mRNA for three trophic factors, basic and acidic fibroblast growth factor (bFGF, aFGF), and nerve growth factor (NGF), after a standardized incomplete thoracic contusive spinal cord injury (SCI). RNase protection assays showed a rapid increase (3-fold) in the content of bFGF mRNA by 6 hours after SCI in tissue that included the injury site. No effect of injury was seen in segments of cervical or lumbar cord. bFGF mRNA at the injury site remained significantly increased at 1 and 7 days after SCI. Further, at 7 days, the increase was anatomically restricted to the rostral portion of the injury site suggesting the involvement of specific pathways in the maintenance of high levels of bFGF mRNA. No change in the levels of aFGF mRNA was seen after SCI. Similarly, no difference in the expression of the mRNA for NGF or its high affinity receptor (trkA), were observed at 6 h, 1 or 7 days following SCI. Our observation of a specific effect of SCI on bFGF mRNA expression supports a speculative hypothesis that bFGF may play a role in the partial recovery of function seen following incomplete contusive spinal cord injury.
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PMID:Increased basic fibroblast growth factor mRNA following contusive spinal cord injury. 801 71

Administration of mesenchymal stem cells (MSCs) improves the recovery from acute kidney injury (AKI). The mechanism may involve paracrine factors promoting proliferation of surviving intrinsic epithelial cells, but these factors remain unknown. In the current study, we found that microvesicles derived from human bone marrow MSCs stimulated proliferation in vitro and conferred resistance of tubular epithelial cells to apoptosis. The biologic action of microvesicles required their CD44- and beta1-integrin-dependent incorporation into tubular cells. In vivo, microvesicles accelerated the morphologic and functional recovery of glycerol-induced AKI in SCID mice by inducing proliferation of tubular cells. The effect of microvesicles on the recovery of AKI was similar to the effect of human MSCs. RNase abolished the aforementioned effects of microvesicles in vitro and in vivo, suggesting RNA-dependent biologic effects. Microarray analysis and quantitative real time PCR of microvesicle-RNA extracts indicate that microvesicles shuttle a specific subset of cellular mRNA, such as mRNAs associated with the mesenchymal phenotype and with control of transcription, proliferation, and immunoregulation. These results suggest that microvesicles derived from MSCs may activate a proliferative program in surviving tubular cells after injury via a horizontal transfer of mRNA.
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PMID:Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. 2199 95

Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human liver stem cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an alpha(4)-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.
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PMID:Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. 1965 Aug 33

Myocardial infarction (MI), a main cause of heart failure, leads to irreversible cardiomyocytes loss and cardiac function impairment. Current clinical treatments for MI are largely ineffective as they mostly aim to alleviate symptoms rather than repairing the injured myocardium. Thus, development of more effective therapies is compelling. This study aims to investigate whether the extracellular vesicles (EVs) carrying specific anti-apoptotic miRNA can be efficiently internalized into myocardium to achieve desired therapeutic outcomes. Methods: EVs were isolated from HEK293T cells overexpressing miRNA-21 (miR21-EVs) and identified. The RNase resistant rate of miR21-EVs was calculated by real-time PCR and compared with liposomes and polyethylenimine (PEI). Confocal laser scanning microscopy was used for visualizing the cellular internalization of miR21-EVs in primary cultured mouse neonatal cardiomyocytes (CMs), H9c2 rat cardiomyoblasts, and human umbilical vein endothelial cells (HUVECs). The effect of miR21-EVs on the expression of PDCD4, a pro-apoptotic protein that plays an important role in regulating myocardial apoptosis, was also evaluated in these three cell types by real-time PCR and Western blot analysis. In vivo, miR21-EVs was directly injected into the infarct zone following ligation of the left anterior descending of coronary artery in mice. The miR21-EVs distribution and blood vessel (capillary and arteriole) density were evaluated by immunofluorescence staining. Fluorescence in situ hybridization of miRNA-21 was also carried out to confirm the miR21-EVs distribution in vitro and in vivo. The protein level of PDCD4 in myocardium was assessed by immunohistochemical staining. The anti-apoptotic effect of miR21-EVs in cardiomyocytes and endothelial cells were measured using TUNEL staining. Four weeks after injection, the cardiac histological and functional recovery was evaluated by histochemistry staining and echocardiography, respectively. Results: In contrast to liposomes and PEI, EVs significantly inhibited miRNA-21 degradation. MiR21-EVs efficiently delivered miRNA-21 into cardiomyocytes and endothelial cells within 4 hours. Exogenous miRNA-21 in turn significantly reduced PDCD4 expression and attenuated cell apoptosis in vitro. Consistently and importantly, in a preclinical MI animal model, miRNA-21-loaded EVs effectively sent miRNA-21 into cardiomyocytes and endothelial cells, drastically inhibited cell apoptosis and led to significant cardiac function improvement. Conclusion: Our results suggest the cell-derived, genetically engineered EVs may be used therapeutically for the delivery of miRNAs for the rescue of MI and may benefit patients in the future.
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PMID:Localized injection of miRNA-21-enriched extracellular vesicles effectively restores cardiac function after myocardial infarction. 3114 48