CIRCULAT EFFECTS ON GENE EXPRESSION IN FIBROBLASTS
783
Table 2. Genes affected by Circulat as a whole but by not individual components Id
Ratio
t-test
Gene symbol
Gene title
239546_at 1552266_at 232963_at 240625_at 220166_at 221703_at 239734_at 215591_at 223501_at 242398_x_at 210457_x_at 204317_at 1557217_a_at 1558469_at 1554785_at 212525_s_at 213120_at 1569201_a_at 232048_at 204159_at 232429_at 209721_s_at 238281_at 206360_s_at 214696_at 233539_at 212980_at 230454_at 208957_at 220153_at 227015_at 223802_s_at 227602_at 223764_x_at 235666_at 1569690_at 228218_at 241413_at 231212_x_at 226125_at 1554786_at 235165_at 210247_at 242681_at 238972_at 230520_at 244700_at 235564_at 243378_at 210222_s_at 229455_at 211916_s_at 235462_at 1558365_at 1559747_at
4.35 2.77 2.67 2.65 2.61 2.26 2.21 2.16 2.09 2.08 2.07 2.04 2 1.92 1.88 1.86 1.71 1.69 1.61 1.55 0.66 0.66 0.66 0.66 0.65 0.64 0.64 0.63 0.63 0.63 0.63 0.62 0.61 0.6 0.6 0.6 0.6 0.59 0.58 0.56 0.55 0.55 0.51 0.5 0.49 0.49 0.47 0.46 0.46 0.44 0.43 0.39 0.38 0.35 0.35
0.01 0.05 0.02 0.03 0.02 0.02 0.05 0.01 0 0.03 0.05 0.02 0.01 0 0.01 0.01 0 0.01 0 0.01 0.01 0.01 5.96E-005 0.01 0.01 0 0.01 0.01 0 0 0 0 0.01 0.01 0.01 0.01 0 0.01 0.01 0 0.01 0.01 0.01 0.02 0.02 0.03 0.02 0.03 0.01 0.01 0 0.03 0 0 0.05
PQLC2 ADAM32 RFWD2 UBE2E3 CNNM1 BRIP1 LOC401320 SATB2 --ATP5F1 HMGA1 GTSE1 FANCB LPP CCDC82 H2AFX KIAA0701 SEC15L2 FAM76B CDKN2C --HOM-TES-103 RBMS1 SOCS3 MGC14376 NAPE-PLD AHSA2 ICA1L TXNDC4 ENTPD7 ASPHD2 RBBP6 RAB7 NIPSNAP3B --CCDC36 --RNF111 TPST1 SLC9A3 C20orf32 PARD6B SYN2 NQO1 --AIG1 SEC61B ZNF117 --RTN1 --MYO1A CPEB2 PGK1 KIAA1840
PQ loop repeat containing 2 ADAM metallopeptidase domain 32 Ring finger and WD repeat domain 2 Ubiquitin-conjugating enzyme E2E 3 (UBC4/5 homolog, yeast) Cyclin M1 BRCA1 interacting protein C-terminal helicase 1 Hypothetical LOC401320 SATB family member 2 --ATP synthase, H+ transporting, mitochondrial F0 complex, subunit B1 High mobility group AT-hook 1 G-2 and S-phase expressed 1 Fanconi anemia, complementation group B LIM domain containing preferred translocation partner in lipoma Coiled-coil domain containing 82 H2A histone family, member X KIAA0701 protein SEC15-like 2 (S. cerevisiae) Family with sequence similarity 76, member B Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) MRNA; cDNA DKFZp434G1972 (from clone DKFZp434G1972) Hypothetical protein LOC25900, isoform 3 RNA binding motif, single stranded interacting protein 1 Suppressor of cytokine signaling 3 Hypothetical protein MGC14376 N-acyl-phosphatidylethanolamine-hydrolysing phospholipase D AHA1, activator of heat shock 90kDa protein ATPase homolog 2 (yeast) Islet cell autoantigen 1,69kDa-like Thioredoxin domain containing 4 (endoplasmic reticulum) Ectonucleoside triphosphate diphosphohydrolase 7 Aspartate beta-hydroxylase domain containing 2 Retinoblastoma binding protein 6 RAB7, member RAS oncogene family Nipsnap homolog 3B (C. elegans) --Coiled-coil domain containing 36 CDNA clone IMAGE:5284125 Ring finger protein 111 Tyrosylprotein sulfotransferase 1 Solute carrier family 9 (sodium/hydrogen exchanger), member 3 Chromosome 20 open reading frame 32 par-6 partitioning defective 6 homolog beta (C. elegans) Synapsin II NAD(P)H dehydrogenase, quinone 1 Transcribed locus Androgen-induced 1 Sec61 beta subunit Zinc finger protein 117 (HPF9) Transcribed locus, moderately similar to NP_060312.1 Reticulon 1 Full length insert cDNA clone YZ04E02 Myosin IA Cytoplasmic polyadenylation element binding protein 2 Phosphoglycerate kinase 1 KIAA1840
with the established ability of Circulat to prevent the development of severe manifestations of type 2 diabetes, which is a complex syndrome involving many intracellular signaling cascades and pathways as well as cell–cell interactions. Many of those pathways are involved in energy generation and are regulated on both transcriptional and post-transcriptional levels in response to endogenous or exogenous stimuli. A high proportion of genes identified in our experiments are implicated in the regulation of transcription (e.g. ATF3, Copyright © 2007 John Wiley & Sons, Ltd.
Kruppel-like factor 4, Zinc finger protein 117, SATB2), energy production and glucose metabolism (thioredoxin domain containing 11, ATP5F1, PGK1) and signal transduction corroborating the hypothesis that Circulat is capable of normalizing molecular processes perturbed in the course of type 2 diabetes. Specifically, Circulat has been proven to be effective in the treatment of diabetic gangrene, which is often resistant to common treatments. Previous studies have suggested that impaired fibroblast function such as proliferation, cell migration, Phytother. Res. 21, 777–789 (2007) DOI: 10.1002/ptr