Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary epithelial cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Death
  • Cell Line
  • Cell Survival
  • Cysteine-Rich Protein 61
  • Gene Expression
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt
  • RNA, Small Interfering
  • Respiratory Distress Syndrome, Adult
  • Signal Transduction

MeSH Major

  • Hyperoxia
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Respiratory Mucosa

abstract

  • We have used gene expression profiling approaches to identify new molecular targets in various models of lung injury and human lung diseases. Among the many genes that are significantly induced in these studies, cysteine-rich61 (Cyr61) consistently ranks as one of the most significant genes. Here, we use the well-established model of hyperoxia to better understand the function of Cyr61 in acute lung injury. Cyr61, a stress-related immediate-early response gene, has known diverse functions involving angiogenesis, tumorigenesis, and wound repair. It belongs to the newly discovered "CCN" family containing six growth and regulatory factors. We showed that hyperoxia induces Cyr61 expression in a variety of pulmonary cells and in lung tissue in vivo. Loss of function studies, by suppressing Cyr61 expression by siRNA, accelerated lung epithelial cell death after hyperoxia. Gain of function studies, by overexpressing Cyr61, significantly conferred increased resistance to hyperoxia-induced cell death. Moreover, cells overexpressing Cyr61 induce Akt activation. Inhibition of Akt by siRNA abrogated the protective effects of Cyr61-overexpressing cells in response to hyperoxia. Taken together, our data demonstrate that Cyr61 expression provides cytoprotection in hyperoxia-induced pulmonary epithelial cell death and that this effect was in part mediated via the Akt signaling pathway.

publication date

  • September 2005

has subject area

  • Animals
  • Cell Death
  • Cell Line
  • Cell Survival
  • Cysteine-Rich Protein 61
  • Gene Expression
  • Humans
  • Hyperoxia
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • RNA, Small Interfering
  • Respiratory Distress Syndrome, Adult
  • Respiratory Mucosa
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2005-0144OC

PubMed ID

  • 15961723

Additional Document Info

start page

  • 297

end page

  • 302

volume

  • 33

number

  • 3