Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using in situ hybridization techniques and RNase protection assays, type II collagen mRNA was transiently detected in the epidermis of chick embryonic skins during days 9-15 after fertilization, with a maximum expression at day 11. Immunohistochemical studies demonstrated that deposition of type II collagen was also transiently localized at the subepidermal region during days 10-15. Type II collagen gene and gene product concomitantly started to decline preferentially at the region where feather buds were being formed on day 12, and thereafter diminished at the region between feather buds. Using immunohistochemical methods, type II collagen was also detected in human fetal scalp skin at 17-23 fetal weeks at the subepidermal region, excluding the region beneath the hair follicles. These results indicate that the lack of type II collagen expression is related to the development of feather and hair at a certain stage of chick embryonic and human fetal skin development.
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PMID:Expression of type II collagen at the middle stages of chick embryonic and human fetal skin development. 800 60

Retinoic acid (RA) has been shown to rapidly modulate the collagen expression pattern of chondrocytes in vitro at doses of 1-10 microM. Embryonic chicken sternal chondrocytes stop synthesizing the cartilage-specific type II collagen within 2-4 days of RA treatment and turn on the synthesis of types I and III collagen and fibronectin. While suppression of type II collagen synthesis and onset of type III collagen and fibronectin synthesis have been shown to be regulated at the transcriptional level, conflicting data are available on a possible post-translational regulation of alpha 1(I) collagen gene expression. In this study we demonstrate by comparing a commonly used alpha 1(I) cDNA probe from the 3' end of the alpha 1(I) mRNA with a newly prepared alpha 1(I) cDNA probe from the 5' end (p1E1) that--in contrast to previous reports--chicken sternal chondrocytes do not contain untranslated alpha 1(I) mRNA which may become translatable after RA treatment. By in situ hybridization we show the absence of cytoplasmic alpha 1(I) mRNA from chondrocytes and its presence in the perichondrium of sternal cartilage. Perichondral cells might have contaminated sternal chondrocyte preparations, explaining low levels of alpha 1(I) mRNA seen by Northern hybridization and RNase protection assays of chicken sternal cartilage mRNA even with the p1E1 probe. We show by Northern hybridization and metabolic labeling with 3H-proline followed by SDS-gel electrophoresis that retinoic acid at 3 microM suppresses type II, IX, and X collagen gene expression within 2 days both at the mRNA and protein level and induces the onset of alpha 1(I), alpha 2(I), and alpha 1(III) expression within 3 days. No expression of CRABP, the cellular retinoic acid binding protein, was seen in RA-treated or control chondrocytes, indicating that CRABP protein is not involved in the RA-induced modulation of the chondrocytes.
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PMID:Alterations of collagen mRNA expression during retinoic acid induced chondrocyte modulation: absence of untranslated alpha 1(I) mRNA in hyaline chondrocytes. 839 38

Several techniques were used to study the co-ordination of mRNA levels for five constituent chains of cartilage collagen fibrils during mouse development. Short cDNA clones were first constructed for mouse and human alpha3(IX) and for mouse proalpha1(XI) collagen mRNA species. Northern analysis of developing mouse embryos revealed that the mRNA species for alpha1, alpha2 and alpha3 chains of type IX collagen peaked earlier than those for proalpha1(II) and proalpha1(XI) collagen chains. Quantification of these mRNA species by slot-blot hybridization confirmed this developmental regulation: the mRNA ratios for type II/type IX/type XI collagens changed from 5.7:1:0.6 (at embryonic day 12.5) to 10.6:1:0.9 (in newborn mice). However, the genes coding for the three chains of type IX collagen seemed to be under more co-ordinated regulation during mouse development. In addition to high mRNA levels in cartilages and the eye, low levels of type IX collagen transcripts were identified in brain and skin of newborn mouse using RNase protection and reverse transcriptase-PCR assays. Finally, hybridization in situ revealed identical tissue distributions of the three type IX collagen mRNA species during early chondrogenesis but somewhat more widespread expression of the alpha1(IX) and alpha3(IX) mRNA species during endochondral ossification at day 16.5 of embryonic development. These results suggest a relatively tight co-ordination of the alpha1(IX), alpha2(IX), and alpha3(IX) collagen mRNA species in chondrocytes, but a lack of co-ordination in several non-cartilaginous tissues.
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PMID:Developmental regulation of mRNA species for types II, IX and XI collagens during mouse embryogenesis. 916 58

Reexpression of aggrecan and type II collagen genes in dedifferentiated adult human articular chondrocytes (AHAC) in suspension culture varied widely depending on the specific lot of bovine serum used to supplement the culture medium. Some lots of serum provided strong induction of aggrecan and type II collagen expression by AHAC while others did not stimulate significant production of these hyaline cartilage extracellular matrix molecules even following several weeks in culture. Addition of 50 ng/ml insulin-like growth factor-I (IGF-I) to a deficient serum lot significantly enhanced its ability to induce aggrecan and type II collagen mRNA. Given this observation, IGF-I and other growth factors were tested in defined serum-free media for their effects on the expression of these genes. Neither IGF-I nor insulin nor transforming growth factor beta (TGF-beta) alone stimulated induction of aggrecan or type II collagen production by dedifferentiated AHAC. However, TGF-beta 1 or TGF-beta 2 combined with IGF-I or insulin provided a strong induction as demonstrated by RNase protection and immunohistochemical assays. Interestingly, type I collagen, previously shown to be downregulated in serum supplemented suspension cultures of articular chondrocytes, persisted for up to 12 weeks in AHAC cultured in defined medium supplemented with TGF-beta and IGF-I.
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PMID:Synergistic action of transforming growth factor-beta and insulin-like growth factor-I induces expression of type II collagen and aggrecan genes in adult human articular chondrocytes. 943 27

Cartilage collagens type II and type IX exist in two alternative forms which arise from alternative splicing and alternative use of promoters, respectively. In the present study we analyzed temporal and spatial expression patterns of the two isoforms of type II and type IX collagen transcripts as well as those of alpha2(IX) and alpha3(IX) collagen mRNAs in limb cartilages and eyes during mouse embryonic development. Northern and RNase protection assays revealed temporal coregulation of the two alternative isoforms in limbs, but not in the eye where no long form of alpha1(IX) collagen mRNA was detected. Although in situ hybridization of limbs revealed identical expression patterns of the long form of type II collagen and the short form of alpha1(IX) collagen mRNA in the perichondrium and periosteum of 14.5-18.5-day embryos, the patterns were distinctly different at day 12.5 of development: the long form of type II collagen mRNA was expressed throughout the developing cartilaginous anlage whereas the short form of alpha1(IX) collagen mRNA was expressed in the surrounding mesenchyme. Some differences were also detected in the temporal and spatial expression patterns between the alpha1(IX), alpha2(IX), and alpha3(IX) collagen mRNAs. In the eyes, alpha2(IX) collagen mRNA had highest expression levels at day 12.5, whereas alpha1(IX) and alpha3(IX) collagen mRNAs peaked later, at day 16.5. In the limbs, alpha1(IX) and alpha3(IX), but not alpha2(IX), collagen mRNAs were detected in periosteal cells after 16.5 days of development. In transgenic Dell mice, harboring type II collagen transgenes with a small deletion mutation, expression of mutant mRNA affected neither the alternative splicing of wild-type or mutant transcripts nor the ratio of the two alternative forms of the alpha1(IX) collagen mRNA. Despite some distinct similarities, the two alternative forms of type II and type IX collagen must, therefore, be under differential control during mouse development.
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PMID:Expression of type II and IX collagen isoforms during normal and pathological cartilage and eye development. 972 Sep 87

Chondrosarcoma is the second most common malignant bone tumor, characterized by production of abundant extracellular matrix resembling hyaline cartilage. To better understand the molecular pathogenesis of chondrosarcoma, we analyzed 12 chondrosarcomas for their production of connective tissue components and SOX9, a key regulator of normal chondrocyte differentiation. Furthermore, 10 chondrosarcoma samples were screened for additional changes in gene expression using cDNA array analysis. In Northern analysis, several tumors were found to express type II collagen mRNA at levels comparable to fetal cartilage used as a control. Interestingly, the highest levels of type II collagen mRNA were seen in 2 of the 3 grade 3 chondrosarcomas, which also exhibited the highest mRNA levels of SOX9 and "prechondrogenic" pro alpha 1(IIA) collagen. Expression of SOX9 in human chondrosarcomas is novel and suggests that chondrosarcomas originate from a multipotent stem cell committed to differentiation along the chondrogenic pathway. Results of the cDNA array analyses emphasize the heterogeneous nature of chondrosarcoma as no single transcript was systematically up- or downregulated in all tumors analyzed. Among the interesting changes observed was upregulation of decorin mRNA in 7 of the 10 tumors analyzed. Further studies are needed to determine whether decorin plays a role in the pathogenesis of chondrosarcoma. The cDNA arrays also revealed discrepancies from Northern and RNase protection analyses in transcript levels of matrix components, emphasizing the need to validate cDNA array data with other techniques.
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PMID:Molecular profiling of human chondrosarcomas for matrix production and cancer markers. 1211 62

A majority of congenital heart defects are due to abnormal development of the valves and membranous septa, i.e., connective tissue components of the heart. During development, an interesting feature of cardiac connective tissue is transient expression of collagens typical for cartilage. To better understand the role of these collagens in the heart, we have performed a systematic study on the temporospatial expression of type II and IX collagen isoforms during mouse heart development employing northern hybridization and RNase protection assay. The mRNAs for alpha1(II) and alpha1(IX) collagens were expressed transiently between embryonic days 10.5 and 14.5 in embryonic mouse heart. RNase protection assays revealed that for both transcripts the embryonic ("prechondrogenic") variants of the alternatively spliced mRNA isoforms dominated. Immunohistochemistry demonstrated that type IIA collagen and Sox9, its key transcriptional regulator, were expressed in the epithelial-mesenchymal areas of the developing heart, with partially overlapping patterns particularly in valvular and septal regions. In addition, Sox9 expression was detected widely in the developing heart. These observations support the hypothesis that cartilage collagens, especially the long isoform of type II collagen, participate in the morphogenesis of cardiac valves and septa.
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PMID:Expression patterns of cartilage collagens and Sox9 during mouse heart development. 1288 5

The transcription factor serum amyloid A-activating factor-1 (SAF-1) has been identified as a regulator of a number of cellular genes. To assess the pleiotropic role of SAF-1 in vivo, we generated SAF-1 transgenic mice, in which CMV immediate-early promoter was used to direct expression of the SAF-1 transgene in multiple organs. Our study shows that overexpression of SAF-1 predisposes animals to arthritis. Although SAF-1 transgenic mice do not spontaneously develop arthritis, they develop a severe form of arthritis when challenged with the Lyme disease agent Borrelia burgdorferi, which is known to promote arthritis development in both humans and mice. CMV-SAF-1 transgenic mice, upon B. burgdorferi infection, showed increased joint swelling and synovial inflammation compared with nontransgenic littermates. Immunohistochemical analysis of joint tissues collected 21 days after B. burgdorferi infection revealed colocalization of matrix metalloproteinase-1, a degradative enzyme that destroys type II collagen, a major architectural component of articular cartilage, and SAF-1 in both SAF-1 transgenic and nontransgenic mice. Further analysis by RNase protection assay and Western immunoblot demonstrated the presence of higher levels of matrix metalloproteinase-1 and SAF-1 in the inflamed joints of SAF-1 transgenic mice compared with their levels in nontransgenic mice. Consistent with these findings, reduced levels of proteoglycans were detected in the inflamed joint cartilage of transgenic mice, indicating damage to the cartilage structure. Together these results suggest a role of SAF-1 in the pathogenesis of inflammation-induced arthritis.
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PMID:Serum amyloid A-activating factor-1 (SAF-1) transgenic mice are prone to develop a severe form of inflammation-induced arthritis. 1538 4