Fibulin‐4 and latent‐transforming growth factor beta‐binding protein‐4 interactions with syndecan‐2 and syndecan‐3 are required for elastogenesis DOI Creative Commons

Hana Hakami,

Neha E. H. Dinesh,

Valentin Nelea

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(7)

Published: April 1, 2025

Abstract Elastogenesis is a cell surface‐located hierarchical process that requires the core components tropoelastin and fibrillins several accessory proteins, including fibulin‐4 (FBLN4) latent TGF‐β binding protein‐4 (LTBP4). FBLN4 LTBP4 interact with cells, but their receptors associated molecular elastogenic mechanisms remain unknown. Primary skin fibroblasts vascular smooth muscle cells bound strongly to multimers monomers. We identified two interaction epitopes on located in cbEGF2‐3 C‐terminal domain, whereas multimerization sites were mapped cbEGF4‐5 domain. also determined novel site N‐terminal half of LTBP4. Cell was inhibited presence heparin, heparan sulfate, or after enzymatic removal suggesting sulfate proteoglycans as relevant surface receptors. siRNA knockdown experiments syndecan (SDC)2 SDC3 for FBNL4 Direct protein interactions between recombinant ectodomains SDC2 SDC3, validated these results. Interaction enhanced elastogenesis, and/or knockdowns led reduced elastic fiber formation. The significantly focal adhesion formation, induced contraction, activation kinase (FAK), Erk1/2, RhoA. Pharmacological inhibition effectors markedly attenuated levels pFAK, pERK, active Together, data demonstrate through promote elastogenesis by enhancing leading contractility FAK, RhoA activation, underscoring significance pathways elastogenesis.

Language: Английский

Fibulin‐4 and latent‐transforming growth factor beta‐binding protein‐4 interactions with syndecan‐2 and syndecan‐3 are required for elastogenesis DOI Creative Commons

Hana Hakami,

Neha E. H. Dinesh,

Valentin Nelea

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(7)

Published: April 1, 2025

Abstract Elastogenesis is a cell surface‐located hierarchical process that requires the core components tropoelastin and fibrillins several accessory proteins, including fibulin‐4 (FBLN4) latent TGF‐β binding protein‐4 (LTBP4). FBLN4 LTBP4 interact with cells, but their receptors associated molecular elastogenic mechanisms remain unknown. Primary skin fibroblasts vascular smooth muscle cells bound strongly to multimers monomers. We identified two interaction epitopes on located in cbEGF2‐3 C‐terminal domain, whereas multimerization sites were mapped cbEGF4‐5 domain. also determined novel site N‐terminal half of LTBP4. Cell was inhibited presence heparin, heparan sulfate, or after enzymatic removal suggesting sulfate proteoglycans as relevant surface receptors. siRNA knockdown experiments syndecan (SDC)2 SDC3 for FBNL4 Direct protein interactions between recombinant ectodomains SDC2 SDC3, validated these results. Interaction enhanced elastogenesis, and/or knockdowns led reduced elastic fiber formation. The significantly focal adhesion formation, induced contraction, activation kinase (FAK), Erk1/2, RhoA. Pharmacological inhibition effectors markedly attenuated levels pFAK, pERK, active Together, data demonstrate through promote elastogenesis by enhancing leading contractility FAK, RhoA activation, underscoring significance pathways elastogenesis.

Language: Английский

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