HSPA12B is predominantly expressed in endothelial cells and required for angiogenesis.
OBJECTIVE
HSPA12B is the newest member of HSP70 family of proteins and is enriched in atherosclerotic lesions. This study focused on HSPA12B expression in mice and its involvement in angiogenesis.


RESULTS
The expression of HSPA12B in mice and cultured cells was studied by: (1) Northern blot; (2) in situ hybridization; (3) immunostaining with HSPA12B-specific antibodies; and (4) expressing Enhanced-Green-Fluorescent-Protein under the control of the HSPA12B promoter in mice. The function of HSPA12B was probed by an in vitro angiogenesis assay (Matrigel) and a migration assay. Interacting proteins were identified through a yeast two-hybrid screening. HSPA12B is predominantly expressed in vascular endothelium and induced during angiogenesis. In vitro angiogenesis and migration are inhibited in human umbilical vein endothelial cells in the presence of HSPA12B-neutralizing antibodies. HSPA12B interacts with multiple proteins in yeast 2-hybrid system.


CONCLUSIONS
We provide the first evidence to our knowledge that the HSPA12B is predominantly expressed in endothelial cells, required for angiogenesis, and interacts with known angiogenesis regulators. We postulate that HSPA12B provides a new mode of angiogenesis regulation and a novel therapeutic target for angiogenesis-related diseases.
Steagall
Rebecca J
RJ
Department of Biochemistry and Molecular Biology, East Tennessee State University, College of Medicine, Johnson City, TN 37614, USA.
Rusiñol
Antonio E
AE
Truong
Quynh A
QA
Han
Zhihua
Z
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001808:Blood Vessels / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014018:Tissue Distribution
D000906:Antibodies; D018840:HSP70 Heat-Shock Proteins; C513783:HSPA12B protein, mouse; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins