Inducible capillary formation in lymphatic endothelial cells by blocking lipid phosphate phosphatase-3 activity.
Lymphangiogenesis plays critical roles under normal and/or pathological conditions; however, the molecular contributors to this event were unknown until recently. In the present study, we first employed gene chip analysis and confirmed that lipid phosphate phosphatase-3 (LPP3) expression was increased until capillary formation in the conditionally immortalized rat lymphatic endothelial cell line. Signaling responses occur when several lipids induce acute biological functions; further, lipid phosphate phosphatases (LPPs) control their functions via dephosphorylation; however, there is no report on the association between LPP3 and lymphangiogenesis. siRNA-targeted LPP3 significantly increased capillary formation of human lymphatic endothelial cells; in contrast, it decreased cell adhesion to the basement membrane matrix. Furthermore, the inducible effect of the LPP inhibitor on capillary formation was observed. For the first time, we report that LPP3 abolishes accelerated abnormal lymphangiogenesis. Blocking LPP3 activities may aid in the development of novel therapy for lymph vessel defects.
Senda
Kazutaka
K
Department of Surgery (I), Faculty of Medicine, University of Toyama, Toyama, Japan.
Koizumi
Keiichi
K
Prangsaengtong
Orawin
O
Minami
Takayuki
T
Suzuki
Shunsuke
S
Takasaki
Ichiro
I
Tabuchi
Yoshiaki
Y
Sakurai
Hiroaki
H
Doki
Yoshinori
Y
Misaki
Takuro
T
Saiki
Ikuo
I
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries; D002448:Cell Adhesion; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000201:enzymology; D042783:Endothelial Cells / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000201:enzymology / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000166:cytology / Q000201:enzymology; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C521833:PLPP3 protein, human; D010711:Phosphatidate Phosphatase