The Angiopoietin-like Factor Cornea-derived Transcript 6 Is a Putative Morphogen for Human Cornea

Peek, Ron; Kammerer, Richard A.; Frank, Stefanie; Otte-Höller, Irene; Westphal, Johan R.

doi:10.1074/jbc.m105746200

Cited by 40 publications

(29 citation statements)

References 24 publications

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“…Angiopoetins are involved in angiogenesis [65], inflammation, and glucose [66] and lipid [67] metabolism. In the cornea, ANGPTL7 may function as negative regulator of angiogenesis, contributing to the avascular properties of the tissue [68], whereas in the human ocular trabecular meshwork cells, it has a role in the organization of the ECM [69]. Thus, we suggest that ANGPTL7 may have a role in maintaining the relatively avascular nature of tendon tissue and in the organisation of the ECM.…”

Section: Discussionmentioning

confidence: 95%

Transcriptome analysis of ageing in uninjured human Achilles tendon

et al. 2015

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IntroductionThe risk of tendon injury and disease increases significantly with increasing age. The aim of the study was to characterise transcriptional changes in human Achilles tendon during the ageing process in order to identify molecular signatures that might contribute to age-related degeneration.MethodsRNA for gene expression analysis using RNA-Seq and quantitative real-time polymerase chain reaction analysis was isolated from young and old macroscopically normal human Achilles tendon. RNA sequence libraries were prepared following ribosomal RNA depletion, and sequencing was undertaken by using the Illumina HiSeq 2000 platform. Expression levels among genes were compared by using fragments per kilobase of exon per million fragments mapped. Differentially expressed genes were defined by using Benjamini-Hochberg false discovery rate approach (P <0.05, expression ratios 1.4 log2 fold change). Alternative splicing of exon variants were also examined by using Cufflinks. The functional significance of genes that showed differential expression between young and old tendon was determined by using ingenuity pathway analysis.ResultsIn total, the expression of 325 transcribed elements, including protein-coding transcripts and non-coding transcripts (small non-coding RNAs, pseudogenes, long non-coding RNAs and a single microRNA), was significantly different in old compared with young tendon (±1.4 log2 fold change, P <0.05). Of these, 191 were at higher levels in older tendon and 134 were at lower levels in older tendon. The top networks for genes differentially expressed with tendon age were from cellular function, cellular growth, and cellular cycling pathways. Notable differential transcriptome changes were also observed in alternative splicing patterns. Several of the top gene ontology terms identified in downregulated isoforms in old tendon related to collagen and post-translational modification of collagen.ConclusionsThis study demonstrates dynamic alterations in RNA with age at numerous genomic levels, indicating changes in the regulation of transcriptional networks. The results suggest that ageing is not primarily associated with loss of ability to synthesise matrix proteins and matrix-degrading enzymes. In addition, we have identified non-coding RNA genes and differentially expressed transcript isoforms of known matrix components with ageing which require further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0544-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 95%

Transcriptome analysis of ageing in uninjured human Achilles tendon

et al. 2015

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“…22 Very little is currently known about this protein, which is present in cornea and is thought to influence deposition of ECM. 30 It is noteworthy that the chromosome location of this gene, 1p36.3-p36.2, is the same locus as GLC3B, a primary congenital glaucoma-associated gene. The identification of the disease-causing gene at this locus is still undetermined.…”

Section: Discussionmentioning

confidence: 98%

Gene and Protein Expression Changes in Human Trabecular Meshwork Cells Treated with Transforming Growth Factor-

Zhao

2004

Investigative Ophthalmology & Visual Science

144

116

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Human trabecular meshwork cells can be subjected to increased levels of TGF-beta for several years as a result of glaucoma. The results indicate that changes in extracellular matrix as well as alterations in cytoskeletal proteins occur in these cells as a result of increased TGF-beta. These results are consistent with changes observed in the trabecular meshwork in glaucoma and suggest that at least some of the histologic alterations observed in the meshwork in glaucoma may be the result of increased TGF-betas.

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“…ANGPTL7 regulates extracellular matrix (ECM) formation [36] and is highly expressed in keratinocytes and is a potent anti-angiogenic factor in the cornea [37]. This protein is also described to inhibit tumour growth in a mouse xenograph model [38] and is required for the regeneration of human hematopoietic stem and progenitor cells (HSPCs) [39, 40]. …”

Section: Introductionmentioning

confidence: 99%

Evolution of the angiopoietin-like gene family in teleosts and their role in skin regeneration

2017

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BackgroundThe skin in vertebrates is a protective barrier and damage is rapidly repaired to re-establish barrier function and maintain internal homeostasis. The angiopoietin-like (ANGPTL) proteins are a family of eight secreted glycoproteins with an important role in skin repair and angiogenesis in humans. In other vertebrates their existence and role in skin remains largely unstudied. The present study characterizes for the first time the homologues of human ANGPTLs in fish and identifies the candidates that share a conserved role in skin repair using a regenerating teleost skin model over a 4-day healing period.ResultsHomologues of human ANGPTL1-7 were identified in fish, although ANGPTL8 was absent and a totally new family member designated angptl9 was identified in fish and other non-mammalian vertebrates. In the teleost fishes a gene family expansion occurred but all the deduced Angptl proteins retained conserved sequence and structure motifs with the human homologues. In sea bream skin angptl1b, angptl2b, angptl4a, angptl4b and angptl7 transcripts were successfully amplified and they were differentially expressed during skin regeneration. In the first 2 days of skin regeneration, re-establishment of the physical barrier and an increase in the number of blood vessels was observed. During the initial stages of skin regeneration angptl1b and angptl2b transcripts were significantly more abundant (p < 0.05) than in intact skin and angptl7 transcripts were down-regulated (p < 0.05) throughout the 4-days of skin regeneration that was studied. No difference in angptl4a and angptl4b transcript abundance was detected during regeneration or between regenerating and intact skin.ConclusionsThe angptl gene family has expanded in teleost genomes. In sea bream, changes in the expression of angptl1b, angptl2b and angptl7 were correlated with the main phases of skin regeneration, indicating the involvement of ANGPTL family members in skin regeneration has been conserved in the vertebrates. Exploration of the fish angptl family in skin sheds new light on the understanding of the molecular basis of skin regeneration an issue of importance for disease control in aquaculture.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0859-x) contains supplementary material, which is available to authorized users.

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The Angiopoietin-like Factor Cornea-derived Transcript 6 Is a Putative Morphogen for Human Cornea

Cited by 40 publications

References 24 publications

Transcriptome analysis of ageing in uninjured human Achilles tendon

Transcriptome analysis of ageing in uninjured human Achilles tendon

Gene and Protein Expression Changes in Human Trabecular Meshwork Cells Treated with Transforming Growth Factor-

Evolution of the angiopoietin-like gene family in teleosts and their role in skin regeneration

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