Article
MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease.
Department of Immunology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Immune Network
12/2011;
11(6):309-23.
DOI:10.4110/in.2011.11.6.309
pp.309-23
Source: PubMed
- Citations (3)
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Cited In (0)
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Article: The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.
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ABSTRACT: Since mature erythrocytes are terminally differentiated cells without nuclei and organelles, it is commonly thought that they do not contain nucleic acids. In this study, we have re-examined this issue by analyzing the transcriptome of a purified population of human mature erythrocytes from individuals with normal hemoglobin (HbAA) and homozygous sickle cell disease (HbSS). Using a combination of microarray analysis, real-time RT-PCR and Northern blots, we found that mature erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes and leukocytes, and contributed the majority of the microRNA expression in whole blood. When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals, we noted a dramatic difference in their microRNA expression pattern. We found that miR-320 played an important role for the down-regulation of its target gene, CD71 during reticulocyte terminal differentiation. Further investigation revealed that poor expression of miR-320 in HbSS cells was associated with their defective downregulation CD71 during terminal differentiation. In summary, we have discovered significant microRNA expression in human mature erythrocytes, which is dramatically altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the global analysis of microRNA expression in circulating erythrocytes can provide mechanistic insights into the disease phenotypes of erythrocyte diseases.PLoS ONE 01/2008; 3(6):e2360. · 4.09 Impact Factor -
Article: MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation.
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ABSTRACT: The discovery of microRNAs (miRNAs) is one of the major scientific breakthroughs in recent years and has revolutionized the way we look at gene regulation. Although we are still at a very early stage in understanding their impact on immunity, miRNAs are changing the way we think about the development of the immune system and regulation of immune functions. MiRNAs are implicated in establishing and maintaining the cell fate of immune cells (e.g. miR-181a and miR-223), and they are involved in innate immunity by regulating Toll-like receptor signaling and ensuing cytokine response (e.g. miR-146). Moreover, miRNAs regulate central elements of the adaptive immune response such as antigen presentation (e.g. miR-155) and T cell receptor signaling (miR-181a). Recent evidence showing altered miRNA expression in chronic inflammatory diseases (e.g. miR-203 and miR-146) suggests their involvement in immune-mediated diseases. Furthermore, miRNAs have been implicated in viral immune escape and anti-viral defense (e.g. miR-196). In this review, we will summarize the latest findings about the role of miRNAs in the development of the immune system and regulation of immune functions and inflammation.Seminars in Cancer Biology 05/2008; 18(2):131-40. · 6.47 Impact Factor -
Article: Nephronophthisis-associated ciliopathies.
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ABSTRACT: Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, represents the most frequent genetic cause of end-stage kidney disease in the first three decades of life. Contrary to polycystic kidney disease, NPHP shows normal or diminished kidney size, cysts are concentrated at the corticomedullary junction, and tubulointerstitial fibrosis is dominant. NPHP can be associated with retinitis pigmentosa (Senior-Løken syndrome), liver fibrosis, and cerebellar vermis aplasia (Joubert syndrome) in approximately 10% of patients. Positional cloning of six novel genes (NPHP1 through 6) as mutated in NPHP and functional characterization of their encoded proteins have contributed to the concept of "ciliopathies." It has helped advance a new unifying theory of cystic kidney diseases. This theory states that the products of all genes that are mutated in cystic kidney diseases in humans, mice, or zebrafish are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, osmotic, and other stimuli to mechanisms of cell-cycle control and epithelial cell polarity. The ciliary theory explains the multiple organ involvement in NPHP regarding retinitis pigmentosa, liver fibrosis, ataxia, situs inversus, and mental retardation. Mutations in NPHP genes cause defects in signaling mechanisms, including the noncanonical Wnt signaling pathway. The "ciliopathy" NPHP thereby is caused by defects in tissue differentiation and maintenance as a result of impaired processing of extracellular cues. Nephrocystins, the proteins that are encoded by NPHP genes, are highly conserved in evolution. Positional cloning of additional causative genes of NPHP will elucidate further signaling mechanisms that are involved, thereby establishing therapeutic approaches using animal models in mouse, zebrafish, and Caenorhabditis elegans.Journal of the American Society of Nephrology 07/2007; 18(6):1855-71. · 9.66 Impact Factor
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Keywords
cellular miRNAs
endometrium diseases
enodmetrium diseases
extensive participation
host cellular miRNA expression profile
human diseases
infectious diseases
kidney diseases
miRNAs
own miRNAs
pathogen infections
pathological conditions
profound impact
Recent studies
RNA viruses
sickle cell disease
small non-coding RNAs
various human diseases
viral gene expression
viral infection