ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines.
We here report the identification of a novel human endothelial cell-specific molecule (called ESM-1) cloned from a human umbilical vein endothelial cell (HUVEC) cDNA library. Constitutive ESM-1 gene expression (as demonstrated by Northern blot and reverse transcription-polymerase chain reaction analysis) was found in HUVECs but not in the other human cell lines tested. The cDNA sequence contains an open reading frame of 552 nucleotides and a 1398-nucleotide 3'-untranslated region including several domains involved in mRNA instability and five putative polyadenylation consensus sequences. The deduced 184-amino acid sequence defines a cysteine-rich protein with a functional NH2-terminal hydrophobic signal sequence. Searches in several data bases confirmed the unique identity of this sequence. A rabbit immune serum raised against the 14-kDa COOH-terminal peptide of ESM-1 immunoprecipitated a 20-kDa protein only in ESM-1-transfected COS cells. Immunoblotting and immunoprecipitation of HUVEC lysates revealed a specific 20-kDa band corresponding to ESM-1. In addition, constitutive ESM-1 gene expression was shown to be tissue-restricted to the human lung. Southern blot analysis suggests that a single gene encodes ESM-1. A time-dependent up-regulation of ESM-1 mRNA was seen after addition of tumor necrosis factor alpha (TNFalpha) or interleukin (IL)-1beta but not with IL-4 or interferon gamma (IFNgamma) alone. In addition, when IFNgamma was combined with TNFalpha, IFNgamma inhibited the TNFalpha-induced increase of ESM-1 mRNA level. These data suggest that ESM-1 may have potent implications in the areas of vascular cell biology and human lung physiology.
Lassalle
P
P
INSERM U416, Institut Pasteur, 1 boulevard A. Calmette, 59000 Lille, France.
Molet
S
S
Janin
A
A
Heyden
J V
JV
Tavernier
J
J
Fiers
W
W
Devos
R
R
Tonnel
A B
AB
D000595:Amino Acid Sequence; D001483:Base Sequence; D016207:Cytokines / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008168:Lung / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015854:Up-Regulation
D016207:Cytokines; D018076:DNA, Complementary; C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger