CSRP1

Cysteine and glycine-rich protein 1 (Cysteine-rich protein 1) (CRP) (CRP1) (Epididymis luminal protein 141) (HEL-141) [CSRP] [CYRP]

Publications

FOXO3, a Molecular Search for the Fountain of Youth.

PubMed

Full text

FOXO3 has been consistently associated with longevity and with a reduction in the prevalence of cardiovascular disease. In this issue, Yan et al. (2019) report that FOXO3-activated vascular cells derived from human embryonic stem cells (ESCs) promote multiple vascular functions and reverse cellular aging through the transcriptional repression of CSRP1.

MeSH Terms

• Adolescent
• Cellular Senescence
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• Humans
• Longevity
• Regeneration

FOXO3-Engineered Human ESC-Derived Vascular Cells Promote Vascular Protection and Regeneration.

PubMed

Full text

FOXO3 is an evolutionarily conserved transcription factor that has been linked to longevity. Here we wanted to find out whether human vascular cells could be functionally enhanced by engineering them to express an activated form of FOXO3. This was accomplished via genome editing at two nucleotides in human embryonic stem cells, followed by differentiation into a range of vascular cell types. FOXO3-activated vascular cells exhibited delayed aging and increased resistance to oxidative injury compared with wild-type cells. When tested in a therapeutic context, FOXO3-enhanced vascular cells promoted vascular regeneration in a mouse model of ischemic injury and were resistant to tumorigenic transformation both in vitro and in vivo. Mechanistically, constitutively active FOXO3 conferred cytoprotection by transcriptionally downregulating CSRP1. Taken together, our findings provide mechanistic insights into FOXO3-mediated vascular protection and indicate that FOXO3 activation may provide a means for generating more effective and safe biomaterials for cell replacement therapies.

MeSH Terms

• Adult
• Animals
• Cell Differentiation
• Disease Models, Animal
• Embryonic Stem Cells
• Endothelial Cells
• Forkhead Box Protein O3
• Genetic Engineering
• Humans
• Ischemia
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• Regeneration

Keywords

• FOXO3
• aging
• gene editing
• stem cell
• vascular cells