MT1-MMP releases latent TGF-β1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1

Tatti, Olga; Vehviläinen, Piia; Lehti, Kaisa; Keski‐Oja, Jorma

doi:10.1016/j.yexcr.2008.05.018

Cited by 133 publications

(112 citation statements)

References 65 publications

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“…43 Similarly, Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) cleaves ECM-bound LTBP-1 to release the large latent TGF-␤1 complex in PMA-treated endothelial cells. 44 A C-terminal fibrillin-1 fragment encoded by exons 44 to 49 disrupts binding of LTBP-1-bound LLC to microfibrils, resulting in the release of TGF-␤1 and increased Smad2 signaling. 45 These studies suggest that solubilization of LLC from the ECM or prevention of LLC targeting to the ECM contributes to latent TGF-␤ activation.…”

Section: Discussionmentioning

confidence: 99%

Latent Transforming Growth Factor-β-Binding Protein-4 Regulates Transforming Growth Factor-β1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin

Zhou

Koli

Hagood

et al. 2009

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 99%

Latent Transforming Growth Factor-β-Binding Protein-4 Regulates Transforming Growth Factor-β1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin

Zhou

Koli

Hagood

et al. 2009

The American Journal of Pathology

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“…In contrast to the avb6 results, avb8-expressing cells release active TGF-b into the medium and must coexpress MT1-MMP to achieve activation. MT1-MMP and avb8 colocalize in cells adhering to LAP1, and MT1-MMP cleaves near LAP's amino terminus (MT1-MMP has also been shown to cleave LTBP-1 and release LLC from the ECM, but it is not known if this action is also important in avb8-mediated activation) (Tatti et al 2008). b8 has a cytoplasmic domain that is not similar to those of other b subunits.…”

Section: Tgf-b Activation By Rgd-binding Integrinsmentioning

confidence: 99%

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Munger¹,

Sheppard²

2011

Cold Spring Harbor Perspectives in Biology

326

275

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The growth factor TGF-b is secreted in a latent complex consisting of three proteins: TGF-b, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-b propeptide) and an ECM-binding protein (one of the latent TGF-b binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-b in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-b through binding this site. Mutant mice defective in integrin-mediated activators, and humans and mice with fibrillin gene mutations, show the critical role of ECM and integrins in regulating TGF-b signaling.

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“…Given the low substrate specificity of many MMPs, however (Chakraborti et al 2003), and the structural similarities between the fibrillins, LTBPs and fibulins, it seems likely that, collectively, fibrillin-and elastindegrading MMPs will be capable of degrading most elastic fibre components. In addition to their roles in directly mediating tissue remodelling via ECM degradation, MMPs also regulate ECM/cell signalling events and MMP-14 (also known as membrane type 1 MMP) has been shown to release bound TGFβ from LTBP-1 (Tatti et al 2008).…”

Section: Degradationmentioning

confidence: 99%

Tissue elasticity and the ageing elastic fibre

Sherratt

2009

AGE

269

189

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The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality.

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MT1-MMP releases latent TGF-β1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1

Cited by 133 publications

References 65 publications

Latent Transforming Growth Factor-β-Binding Protein-4 Regulates Transforming Growth Factor-β1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin

Latent Transforming Growth Factor-β-Binding Protein-4 Regulates Transforming Growth Factor-β1 Bioavailability for Activation by Fibrogenic Lung Fibroblasts in Response to Bleomycin

Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix

Tissue elasticity and the ageing elastic fibre

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