Knockdown of moesin expression accelerates cellular senescence of human dermal microvascular endothelial cells.
OBJECTIVE
Endothelial cells maintain the homeostasis of blood, which consists of plasma and cellular components, and regulate the interaction between blood and the surrounding tissues. They also have essential roles in vascular permeability, the circulation, coagulation, inflammation, wound healing, and tissue growth. The senescence of endothelial cells is closely related to the aging of the adjacent tissues and to age-related vascular disease. Recently, the expression of moesin was found to be decreased in elderly human dermal microvascular endothelial cells (HDMECs), and an association between moesin and senescence has been suggested. This study examined the functional role of moesin in cellular senescence.


METHODS
To study the effects of decreased moesin expression on cellular senescence and metabolism, HDMECs were transfected with short hairpin-RNA (shRNA) lentivirus to silence moesin gene expression. In addition, specimens from young and old human skin were stained with antimoesin and anti-p16 antibodies as an in vivo study.


RESULTS
Using shRNAlentivirus, moesin knock-down HDMECs developed characteristics associated with aging and expressed senescence associated-beta-galactosidase during early passages. They also showed increased p16 expression, decreased metabolic activity, and cell growth retardation. Human skin tissue from elderly persons showed decreased moesin expression and increased p16 expression.


CONCLUSIONS
These findings suggest that there is a functional association between moesin expression and cellular senescence. Further study of the functional mechanism of moesin in the cytoskeleton and cellular senescence is needed. In addition, this study provides a useful model for developing anti-aging treatments.
Lee
Ju Hee
JH
Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seodaemun-gu, Seoul 120-752, Korea.
Yoo
Jung Hoan
JH
Oh
Sang Ho
SH
Lee
Kyu-Yeop
KY
Lee
Kwang Hoon
KH
D000369:Aged, 80 and over; D015153:Blotting, Western; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D002648:Child; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008858:Microscopy, Phase-Contrast; D055806:Microvessels / Q000166:cytology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply*
D008840:Microfilament Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; C071058:moesin