title: Role of connective tissue growth factor in extracellular matrix degradation in renal tubular epithelial cells.
abstract: In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor beta1 (TGF-beta1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-beta1 (5 microg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-beta1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-beta1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.
authors: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Chun
authors: C
authors: Zhang
authors: Zhonghua
authors: Z
authors: Zhu
authors: Jianshe
authors: J
authors: Liu
authors: Xiao
authors: X
authors: Yang
authors: Ling
authors: L
authors: Fu
authors: Anguo
authors: A
authors: Deng
mesh_terms: D002460:Cell Line; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor