Cross Talk among TGF- Signaling Pathways, Integrins, and the Extracellular Matrix
Open accessAbstract
The growth factor TGF-β is secreted in a latent complex consisting of three proteins: TGF-β, an inhibitor (latency-associated protein, LAP, which is derived from the TGF-β propeptide) and an ECM-binding protein (one of the latent TGF-β binding proteins, or LTBPs). LTBPs interact with fibrillins and other ECM components and thus function to localize latent TGF-β in the ECM. LAP contains an integrin-binding site (RGD), and several RGD-binding integrins are able to activate latent TGF-β 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-β signaling.
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Integrin αvβ8, composed of Itgb8 and Itgav subunits, plays a critical role in TGFβ activation and microglia homeostatic maturation.
“subunits of integrin α v β8 (ref. 30; Fig. 6b,c and Supplementary Table 5), which plays a critical role in TGFβ activation and microglia homeostatic maturation 31”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [30]
The section “TGF-b Activation by RGD-Binding Integrins” (page unavailable) says that αvβ8 activates TGF-β1 and TGF-β3. Our copy does not address microglial homeostatic maturation, so it supports the activation claim but not that additional role. (LLM, conf=0.88)
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Cites
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Flagged first, then by citations
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From Structure to Phenotype: Impact of Collagen Alterations on Human Health
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“One representative example is the TGFβ proteins, which indirectly connect to fibrillins and fibronectins [18] and are stored in the ECM in their inactive form until proteolitically activated by matrix metalloproteinases (MMP) or by mechanical forces.”
BackgroundTGFβ2 and TGFβ3 isoforms drive fibrotic disease pathogenesis
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- Authors
- Munger, J. S., & Sheppard, D.
- Affiliations
- New York University (US)
- University of California, San Francisco (US)
- Corresponding author
- Munger, J. S.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-09-07
- Volume
- 3
- Issue
- 11
- Pages
- a005017-a005017
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC3220354
- OpenAlex
- W2140256258
- Cited by
- 372
- References
- 4
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 28 · 2023: 26 · 2022: 30 · 2021: 30 · 2020: 30 · 2019: 24 · 2018: 21 · 2017: 25 · 2016: 25 · 2015: 22 · 2014: 27 · 2013: 25 · 2012: 13
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- TGF-beta signaling, latent TGF-beta, latency-associated protein, latent TGF-beta binding protein, fibrillin, extracellular matrix, integrins, RGD motif
- MeSH terms
- Fibrillins, Animals, Extracellular Matrix, Humans, Marfan Syndrome, Microfilament Proteins, Models, Biological, Signal Transduction, Integrins, Transforming Growth Factor beta, Mice, Latent TGF-beta Binding Proteins
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