Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis

Pellicoro, Antonella; Aucott, Rebecca L.; Ramachandran, Prakash; Robson, Andrew; Fallowfield, Jonathan; Snowdon, Victoria; Hartland, Stephen N.; Vernon, Madeleine A.; Duffield, Jeremy S.; Benyon, R. Christopher; Forbes, Stuart J.; Iredale, John P.

doi:10.1002/hep.25567

Cited by 170 publications

(155 citation statements)

References 33 publications

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“…The obtained results revealed the presence of one parent with fresh prepared protein band and two degraded bands (»55-and »45 kDa) with stored protein (Chen et al, 2005;Pellicoro et al, 2012). The first band at »70 kDa represents the recombinant tropoelastin protein while the other two bands at represent the degraded form of the protein.…”

Section: Discussionmentioning

confidence: 87%

Expression of synthetic human tropoelastin (hTE) protein inNicotiana tabacum

et al. 2015

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ABSTRACT. Plant molecular farming (PMF) is an important growing prospective approach in plant biotechnology; it includes production of recombinant pharmaceutical and industrial proteins in large quantities from engineered plants. Elastin is a major protein component of tissues that require elasticity, it helps keep skin smooth as it stretches to allow normal. Elastin is used as a raw material for the cosmetic industry. In this work, we aimed to use plant as a bioreactor for the expression and production of the full human tropoelastin protein. Agrobacterium-mediated transient expression system into Nicotiana tabacum using syringe agroinfiltration was used to provide fast and convenient way to produce recombinant proteins with greater expression overall the plant leaf. This study aimed to establish an efficient and rapid system for transiently expression and production of human recombinant tropoelastin protein in transgenic N. tabacum plants. Modified elastin (ELN) gene was biosynthesized and cloned into pCambia1390 vector to be used into N. tabacum agroinfilteration. Optimization of codon usage for the human tropoelastin gene, without changing the primary structure of the protein was carried out to ensure high expression in tobacco plants. The obtained data proved that the 5 th day post-infiltration is the optimum interval to obtain the maximum production of our recombinant protein. Southern blot analysis was able to detect 2175 bp fragment length representing the ELN orf (open reding frame). On the other hand, ELN -expression within plant's tissue was visualized by RT-PCR during the period 3-10 days post agroinfiltration. At the protein level, western and ELISA confirmed the expression of recombinant tropoelastin protein. Western blot analysis detected the tropoelastin protein as parent band at »70 kDa from freshly extracted protein, while two degraded bands of »55 and »45 kDa, representing a pattern of tropoelastin were appeared with frozen samples. This study showed that biosynthetic ELN gene was successfully expressed into N. tabacum leaves using agroinfiltration technique.

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Section: Discussionmentioning

confidence: 87%

Expression of synthetic human tropoelastin (hTE) protein inNicotiana tabacum

et al. 2015

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“…66 Interestingly, these mice did not exhibit difference in overall fibrosis compared to control animals if treated by CCL 4 , although increased perisinusoidal elastin was still detected. This points to a distinct mode of action of toxins used to induce fibrosis.…”

mentioning

confidence: 86%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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“…In recent years it has become increasingly clear that tissue repair and remodeling are highly dynamic processes, resulting in continuous synthesis and turnover of ECM components during hepatofibrogenesis, and in disease state-specific changes in both the quantitative amount and qualitative composition of the ECM. 1 In the June 2012 issue of HEPATOLOGY, Pellicoro et al 2 elegantly demonstrate that elastin accumulation represents a distinct feature of advanced-stage liver fibrosis, because of both increased synthesis and decreased macrophage metalloelastase (MMP12)-mediated degradation. Taking these findings, and the results recently reported by Polasek et al 3 on a collagen-specific magnetic resonance (MR) contrast agent into account, we reasoned that elastin might be a promising novel target for molecular MR monitoring of ECM-remodeling during hepatic fibrosis.…”

Section: Elastin-based Molecular Mri Of Liver Fibrosismentioning

confidence: 99%

“…1 Liver biopsy is still the gold standard in evaluating and staging liver fibrosis and cirrhosis. 2 However, it is costly and invasive, with possible complications and sampling variability. Therefore, a number of direct and indirect noninvasive diagnostic tools have been investigated.…”

Section: Replymentioning

confidence: 99%