EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation

Carla Danussi, Alessandra Petrucco, Bruna Wassermann, Eliana Pivetta, Teresa Maria Elisa Modica, Lisa Del Bel Belluz, Alfonso Colombatti, Paola Spessotto

Research output: Contribution to journalArticle

Abstract

EMILIN1 promotes α4β1 integrin-dependent cell adhesion and migration and reduces pro-transforming growth factor-β processing. A knockout mouse model was used to unravel EMILIN1 functions in skin where the protein was abundantly expressed in the dermal stroma and where EMILIN1-positive fibrils reached the basal keratinocyte layer. Loss of EMILIN1 caused dermal and epidermal hyperproliferation and accelerated wound closure. We identified the direct engagement of EMILIN1 to α4β1 and α9β1 integrins as the mechanism underlying the homeostatic role exerted by EMILIN1. The lack of EMILIN1-α4/β9 integrin interaction was accompanied by activation of PI3K/Akt and Erk1/2 pathways as a result of the reduction of PTEN. The downregulation of PTEN empowered Erk1/2 phosphorylation that in turn inhibited Smad2 signaling by phosphorylation of residues Ser245/250/255. These results highlight the important regulatory role of an extracellular matrix component in skin proliferation. In addition, EMILIN1 is identified as a novel ligand for keratinocyte α9β1 integrin, suggesting prospective roles for this receptor-ligand pair in skin homeostasis.

Original languageEnglish
Pages (from-to)131-145
Number of pages15
JournalJournal of Cell Biology
Volume195
Issue number1
DOIs
Publication statusPublished - Oct 3 2011

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Keratinocytes
Integrins
Fibroblasts
Skin
Phosphorylation
Ligands
Transforming Growth Factors
Phosphatidylinositol 3-Kinases
Knockout Mice
Cell Adhesion
Cell Movement
Extracellular Matrix
Homeostasis
Down-Regulation
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Danussi, C., Petrucco, A., Wassermann, B., Pivetta, E., Modica, T. M. E., Belluz, L. D. B., ... Spessotto, P. (2011). EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. Journal of Cell Biology, 195(1), 131-145. https://doi.org/10.1083/jcb.201008013

EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. / Danussi, Carla; Petrucco, Alessandra; Wassermann, Bruna; Pivetta, Eliana; Modica, Teresa Maria Elisa; Belluz, Lisa Del Bel; Colombatti, Alfonso; Spessotto, Paola.

In: Journal of Cell Biology, Vol. 195, No. 1, 03.10.2011, p. 131-145.

Research output: Contribution to journalArticle

Danussi, C, Petrucco, A, Wassermann, B, Pivetta, E, Modica, TME, Belluz, LDB, Colombatti, A & Spessotto, P 2011, 'EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation', Journal of Cell Biology, vol. 195, no. 1, pp. 131-145. https://doi.org/10.1083/jcb.201008013
Danussi C, Petrucco A, Wassermann B, Pivetta E, Modica TME, Belluz LDB et al. EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. Journal of Cell Biology. 2011 Oct 3;195(1):131-145. https://doi.org/10.1083/jcb.201008013
Danussi, Carla ; Petrucco, Alessandra ; Wassermann, Bruna ; Pivetta, Eliana ; Modica, Teresa Maria Elisa ; Belluz, Lisa Del Bel ; Colombatti, Alfonso ; Spessotto, Paola. / EMILIN1-α4/α9 integrin interaction inhibits dermal fibroblast and keratinocyte proliferation. In: Journal of Cell Biology. 2011 ; Vol. 195, No. 1. pp. 131-145.
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