ABSTRACT
The heart failure (HF) diseaseasome is marked by substantial alteration in networked signaling pathways. Reductionist paradigm HF investigative approaches have focused on the regulation of a single pathway or single pathway components. In support of a more comprehensive systems biology investigative paradigm, rapidly evolving experimental evidence supports extensive regulatory cross-talk between the TGF-superfamily, Wnt/-catenin and Hippo signaling systems in homeostasis, myocardial development and a variety of non-myocardial diseases. After reviewing the basic components and integrated regulation of each of these three pathways, we review landmark studies in diverse conditions and diseases highlighting the likely critical importance of regulatory cross-talk between these three pathways in the HF.
ABSTRACT
Background and purpose:DOC-2 serves as one of the tumor suppressing genes in human ovarian cancer and plays a role in the process of cell growth and differentiation.This study was to investigate the role of DOC-2 in the TGF? signal pathway and verification of the interaction between DOC-2 and TGF?Ⅲ receptor.Methods:The bait vector was constructed by inserting the PID domain of DOC-2(nDOC-2)into yeast express vector pGBKT7.pGBKT7-nDOC2 was transformed into the yeast AH109 and confirmed to be expressed.After the human foetus brain cDNA library had been transformed,the positive clones was screened by both nutrition defect medium and X-?-gal.The putative positive clones were sequenced and analyzed to get the DOC-2 interactive proteins.Furthermore,after the DOC-2 cDNA and TGF?Ⅲ receptor cDNA had been co-transfected into the human ovarian cancer cell line HO-8910 together,the interaction between DOC-2 and TGF?Ⅲ receptor was investigated by immunoprecipitation and Western blot.Results:21 putative positive clones were picked after being screened and sequenced.Three of them were identified as Homo sapiens partial mRNA for betaglycan(TBR Ⅲ gene),homo sapiens protocadherin gamma subfamily C3(PCDHGC3)and APLP1(amyloid beta precursor-like protein 1).The analysis by immunoprecipitation and Western blot showed that the interaction between DOC-2 and TGF?Ⅲ receptor could form protein complex.Conclusions:The three encoding proteins might participate in the DOC-2 signal pathway.DOC-2 might play as an essential role in the TGF?signal pathway by interacting with TGF?Ⅲ receptor.