Chromogranin A binds to αvβ6-integrin and promotes wound healing in mice

Flavio Curnis, Anna Maria Gasparri, Renato Longhi, Barbara Colombo, Silvia D'Alessio, Fabio Pastorino, Mirco Ponzoni, Angelo Corti

Research output: Contribution to journalArticlepeer-review

Abstract

Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, neurons, cardiomyocytes, and keratinocytes, is the precursor of various peptides that regulate the carbohydrate/lipid metabolism and the cardiovascular system. We have found that CgA, locally administered to injured mice, can accelerate keratinocyte proliferation and wound healing. This biological activity was abolished by the Asp 45Glu mutation. CgA and its N-terminal fragments, but not the corresponding Asp 45Glu mutants, could selectively recognize the αvβ6-integrin on keratinocytes (a cell-adhesion receptor that is up-regulated during wound healing) and regulate keratinocyte adhesion, proliferation, and migration. No binding was observed to other integrins such as αvβ3, αvβ5, αvβ8, α5β1, α1β1, α3β1, α6β4, α6β7 and α9β1. Structure-activity studies showed that the entire CgA 39-63 region is crucial for avb6 recognition (Ki = 7 nM). This region contains an RGD site (residues CgA 43-45) followed by an amphipathic α-helix (residues CgA 47-63), both crucial for binding affinity and selectivity. These results suggest that the interaction of the RGD/a-helix motif of CgA with αvβ6 regulates keratinocyte physiology in wound healing.

Original languageEnglish
Pages (from-to)2791-2803
Number of pages13
JournalCellular and Molecular Life Sciences
Volume69
Issue number16
DOIs
Publication statusPublished - Aug 2012

Keywords

  • αv/β6 Integrin
  • Chromogranin-A
  • Vasostatin-1
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

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