Cyr61 Protects against Hyperoxia-Induced Cell Death via Akt Pathway in Pulmonary Epithelial Cells
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.
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CCN1 promotes endothelial cell survival through integrin αvβ3 and inhibits apoptosis by activating Akt in pulmonary epithelial cells or upregulating XIAP in MCF7 breast cancer cells.
“CCN1 promotes the survival of endothelial cells through integrin αvβ3 [72], and inhibits apoptosis by activation of Akt in pulmonary epithelial cells [80] or upregulation of XIAP in MCF7 breast cancer cells [81].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [80]
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CCN1/CYR61: the very model of a modern matricellular protein
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- Authors
- Jin, Y., Kim, H. P., Ifedigbo, E., Lau, L. F., & Choi, A. M. K.
- Affiliations
- University of Pittsburgh (US)
- Houston Methodist (US)
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-09-01
- Volume
- 33
- Issue
- 3
- Pages
- 297-302
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W2017736914
- Cited by
- 48
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 8 · 2012: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Keywords
- CYR61, CCN family, hyperoxia, acute lung injury, lung epithelial cells, cell death, Akt signaling, cytoprotection, siRNA knockdown, gene overexpression, lung injury
- MeSH terms
- Animals, Cell Line, Cell Survival, Humans, Mice, Inbred C57BL, Proto-Oncogene Proteins, Respiratory Distress Syndrome, Signal Transduction, Gene Expression, Cell Death, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Hyperoxia, Respiratory Mucosa, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Proto-Oncogene Proteins c-akt, Mice, Cysteine-Rich Protein 61
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