RRP12 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KLF4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
SAMSN1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IL7R UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MXD1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KAZN DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
PPFIBP1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ADRB2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
SCAF11 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
EREG UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
TSC22D2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NFKBID UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZNF101 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
TNFAIP3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CD83 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
TYROBP UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IL1A UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CCL4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
PROX1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CCL5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CD163 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CGA UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ADAMDEC1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
FOS UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KCNJ2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
TNFSF15 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NR4A2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MRC1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CXCL2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ERN1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DAB2 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
DDIT3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
PTHLH UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ADAMTS1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
TNFAIP6 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
REL UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KLF2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NFATC2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NR4A3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RCAN1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
EGR1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ETV3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZBTB10 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NUAK2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MPEG1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
S100A9 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RBBP6 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DUSP10 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ITGB2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) HUVECs normal Control, biological rep4
C14orf132 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
GPR183 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DUSP5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RP4-575N6.4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CCRN4L UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
FZD8 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
EGR3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
FCER1G UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MAFF UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RALGAPA2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ADAMTS5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) HUVECs normal Control, biological rep2
CSRNP1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NLRP3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
In vertebrates, non-lens bg-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive.A naturally existing 72-kDa complex of non-lens bg-crystallin (a-subunit) and trefoil factor (b-subunit), named bg-CAT, was identified from frog Bombina maxima skin secretions. Its a-subunit and b-subunit (containing three trefoil factor domains), with a non-covalently linked form of ab2, show significant sequence homology to ep37 proteins, a group of non-lens bg-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. The bg-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of bg-CAT (25-50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC50 10 nM) and apoptosis. The bg-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membraneÃÂ¯ÃÂÃÂ®. However, what exactly target of bg-CAT act on HUVECs nuclear is still unknown. Primary cultured HUVECs treated with bg-CAT (25 nM, 2 h) were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genome wide level of significant differential gene expression induced by bg-CAT on HUVECs in order to get clues about bg-CAT action mechanisms. These findings illustrate novel cellular functions of non-lens bg-cyrstallins and action mechanism via association with trefoil factors, serving as clues for investigating the possible occurrence of similar molecules and action mechanisms in mammals. Experiment Overall Design: We used microarrays to analysis genome wide level of significant differential gene expression induced by bg-CAT on HUVECs.Four independent biological replicates of HUVECs treated with bg-CAT (25 nM, 2 h) were compared with normal control by SAM. The significant differential expression of 123 genes (fold changeÃÂ¢ÃÂÃÂ¥3, q value =0, FDR (false discovery rate)=0). 121 genes were up-regulated, among which members of nuclear receptor subfamily 4 (NR4A) were the most prominent. Only 2 genes were down-regulated (including collagen type I) (Supporting information Fig. S1 and Table S1 in accompanying publication). Members of NR4A exhibit differential roles in determining cell growth or cell death depending on its location in the nucleus or mitochondria. NR4A1 (also called Nur77, TR3) mediates cell apoptosis through translocation from nucleus to mitochondria and induction of cytochrome c releasing . Significant activation of NR4A members suggests these orphan nuclear receptors may be involved in the mediation of bg-CAT biological functions, like proapoptotic action of the protein at high concentrations. Up-regulated expression of a number of matrix metalloproteinases by bg-CAT could facilitate cell migration and detachment. The bg-CAT also induced the expression of a number of cytokines, including interleukin 1, interleukin 8 and interleukin 6, as well as various chemokines in HUVECs. These data provide clues for study in detail of molecular pathways through which bg-CAT exerts its biological functions.
IL1B UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
JMJD1C UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CXCL3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) bg-CAT treated HUVECs, biological rep1
C11orf96 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CREM UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
INSIG1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZNF785 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
TSC22D1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
BIRC3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) HUVECs normal Control, biological rep3
ICAM1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ACP5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MCL1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
BCL2A1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
JUN UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
LINC00936 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
HES1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
PLAU UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KDM6B UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RRAD UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
SYNE1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NR4A1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
EGR4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CEBPD UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IRAK2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
LIF UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NEAT1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ADM UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DUSP6 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
PMAIP1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KLF10 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
SMAD9 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
KMO UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
HLX UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZNF542P DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
BHLHE40 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
GAS1 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
NFKBIZ UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MMP9 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RGS2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ARG2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CXCL8 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
GTF2H2C DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
SERPINB2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
B3GNT5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
FOSB UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CD44 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IGFBP5 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZNF573 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
MGP DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZC3H12A UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
KITLG UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CYBB UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) bg-CAT treated HUVECs, biological rep4
ARL5B UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
APOLD1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
FGFR3 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
S100A8 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DUSP1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CHAC1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
SPP1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
TRIB1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IL6 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ANKRD10-IT1 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
SOD2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NFKBIA UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
IL1RN UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MLF1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
NKX3-1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
Analysis of 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) HUVECs normal Control, biological rep1
KYNU UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ATF3 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CCL20 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ZFP36 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
MS4A7 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
(Assay) bg-CAT treated HUVECs, biological rep3
(Assay) bg-CAT treated HUVECs, biological rep2
CSF2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
AIF1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
PER1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
CXCR4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
DDIT4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
G0S2 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
LPHN1 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
RDH13 DOWN in 'bg-CAT 25 nanonmolar' vs 'PBS'
CREB5 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
STC1 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
ISG20 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'
RP11-489E7.4 UP in 'bg-CAT 25 nanonmolar' vs 'PBS'