Age-dependent changes in the mechanical properties of tail tendons in TGF-β inducible early gene-1 knockout mice

Bensamoun, Sabine F.; Tsubone, Tetsu; Subramaniam, Malayannan; Hawse, John R.; Boumediene, Emir; Spelsberg, Thomas C.; An, Kai Nan; Amadio, Peter C.

doi:10.1152/japplphysiol.00800.2005

Cited by 32 publications

(39 citation statements)

References 19 publications

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“…KLF10 suppresses cell proliferation, induce apoptosis, and modulate immune system [18,21,22,54]. Although KLF10 deficient mice are reported to grow and reproduce normally [55], these mice demonstrate defects in healing potential [56,57], and abnormally enhanced T cell function resulting in aggravated atherosclerosis [54]. A transcriptome profiling study using the liver of KLF10 deficient mice reveals that KLF10 has a significant role in regulating genes that are involved in lipid and carbohydrate metabolism [23].…”

Section: Discussionmentioning

confidence: 99%

Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of kruppel-like-factor 10 in mice

et al. 2014

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BackgroundKruppel-like-factor (KLF) 10 is identified as transforming growth factor (TGF) β inducible early gene and is reported to suppress lipogenic genes. Although previous studies report that TGFβ plays an important role in progression of nonalcoholic steatohepatitis (NASH) by regulating liver fibrosis, the association of KLF10 and NASH has never been explored. Thus we evaluated expressions and changes of KLF10 in diet induced NASH and in NASH which was alleviated by ursodeoxycholic acid (UDCA). We also assessed KLF10 in quiescent and activated hepatic stellate cells (HSCs).MethodsC57BL/6 mice were given high fat, sucrose diet (HFSD) at least for 12 weeks up to 48 weeks and sacrificed at 12, 24 and 48 weeks thereafter. In other groups, either standard diet (SD) or HFSD was given for 24 weeks at which point mice fed with HFSD were divided into two groups, and were given either UDCA in combination with HFSD or vehicle with HFSD. Mice under SD were given vehicle. HSCs were isolated from C57BL/6 mice in order to evaluated KLF10 expression in activated HSCs.ResultsThe mice were found to acquire liver steatosis and inflammation starting from week 12 of HFSD feeding, although significant liver fibrosis was noticed by week 24. Increased TGFβ and collagen α1(I) (Col1α(I)) expression was also apparent from week 24. However, expression of KLF10 mRNA started to increase from week 12, earlier than TGFβ gene. Up-regulation of KLF10 was accompanied by suppressed carbohydrate response element-binding protein (ChREBP) that is known to be protective against insulin resistance. The mice fed with HFSD and UDCA had decreased Colα(I) mRNA that was coincided with reduced TGFβ and KLF10 expression. Expression of ChREBP was also recovered by UDCA administration. Enhanced KLF10 was noticed in activated HSCs when quiescent cell showed minimal expression.ConclusionsOur study demonstrated that KLF10 expression was significantly increased in diet induced NASH and collagen producing activated HSCs. We also noticed that this up-regulation of KLF10 was accompanied by increased TGFβ signaling genes and suppressed ChREBP expression. These observations suggest possible association of KLF10 and NASH progression.

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Section: Discussionmentioning

confidence: 99%

Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of kruppel-like-factor 10 in mice

et al. 2014

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“…The maximum failure load and the linear stiffness of the composite were measured with a custom-made microtester, 26 which was composed of a linear servo motor (MX 80 Daedal, Irwin, PA) and a load cell with the accuracy of 0.01 N (MDB-5, Transducer Techniques, Temecula, CA). The composites with BMSC from eight dogs after 7- and 14-days incubation were used.…”

Section: Methodsmentioning

confidence: 99%

Multilayer tendon slices seeded with bone marrow stromal cells: A novel composite for tendon engineering

Omae

Zhao

Sun

et al. 2008

Journal Orthopaedic Research

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100

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The ideal scaffold for tendon engineering would possess the basic structure of the tendon, native extracellular matrix, and capability of cell seeding. The purpose of this study was to assess the tissue engineering potential of a novel composite consisting of a decellularized multilayer sliced tendon (MST) scaffold seeded with bone marrow stromal cells (BMSC). BMSC and infraspinatus tendons were harvested from 20 dogs. The tendons were sectioned in longitudinal slices with a thickness of 50 µm. The slices were decellularized, seeded with BMSC, and then bundled into one composite. The composite was incubated in culture media for 14 days. The resulting BMSC-seeded MST was evaluated by qRT-PCR and histology. The BMSC viability was assessed by a fluorescent tracking marker. Histology showed that the seeded cells aligned between the collagen fibers of the tendon slices. Analysis by qRT-PCR showed higher tenomodulin and MMP13 expression and lower collagen type I expression in the composite than in the BMSC before seeding. BMSC labeled with fluorescent tracking marker were observed in the composite after culture. Mechanical testing showed no differences between scaffolds with or without BMSC. BMSC can survive in a MST scaffold. The increased tenomodulin expression suggests that BMSC might express a tendon phenotype in this environment. This new composite might be useful as a model of tendon tissue engineering.

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“…Several studies have shown that TIEG transcription factors in humans and mice are involved in cellular growth control and pancreatic cancer, and biochemical characterization have demonstrated that TIEGs are transcriptional repressors (Cook et al 1998(Cook et al , 1999Cook and Urrutia 2000). Moreover, recent studies on TIEG1 knock-out mice have shown that this gene is involved in flexor tendon healing, cardiac hypertrophy, and skeletal development and maintenance (Bensamoun et al 2006;Tsubone et al 2006;Rajamannan et al 2007). Further analyses will be required to demonstrate whether the proteins identified in this study could play a similar role than TIEGs in humans or mice.…”

Section: Analysis Of Cabut Orthologs In Vertebratesmentioning

confidence: 99%

Identification and analysis of cabut orthologs in invertebrates and vertebrates

2007

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Cabut (cbt) is a Drosophila melanogaster gene involved in epidermal dorsal closure (DC). Its expression is dependent on the Jun N-terminal kinase (JNK) cascade, and it functions downstream of Jun regulating dpp expression in the leading edge cells. The Cbt protein contains three C(2)H(2)-type zinc fingers and a serine-rich domain, suggesting that it functions as a transcription factor. We have identified single cbt orthologs in other Drosophila species, as well as in other insects and invertebrate organisms like ascidians and echinoderms, but not in nematodes. Gene structure and protein sequence are highly conserved among Drosophilidae, but are more diverged in the other species of invertebrates analyzed. According to this, we demonstrate that cbt expression is detected in the embryonic lateral epidermis in several Drosophila species, as it occurs in D. melanogaster, thus suggesting that the cbt orthologs may have a conserved role in these species during DC. We have also analyzed the genomes of several vertebrate species, finding that the cbt orthologous genes in these organisms encode proteins that belong to the TIEG family of Sp1-like/Krüppel-like transcription factors. Phylogenetic analysis of the invertebrate and vertebrate proteins identified indicates that they mainly follow the expected phylogeny of the species, and that the cbt gene was duplicated during vertebrate evolution. Because we were not able to identify cbt orthologous genes neither in yeast nor in plants, our results suggest that this gene has been probably conserved throughout metazoans and that it may play a fundamental role in animal biology.

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Age-dependent changes in the mechanical properties of tail tendons in TGF-β inducible early gene-1 knockout mice

Cited by 32 publications

References 19 publications

Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of kruppel-like-factor 10 in mice

Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of kruppel-like-factor 10 in mice

Multilayer tendon slices seeded with bone marrow stromal cells: A novel composite for tendon engineering

Identification and analysis of cabut orthologs in invertebrates and vertebrates

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