OPEN IN READ APP
JOURNAL ARTICLE

Connective tissue growth factor knockdown attenuated matrix protein production and vascular endothelial growth factor expression induced by transforming growth factor-beta1 in cultured human peritoneal mesothelial cells

Li Xiao, Lin Sun, Fu-You Liu, You-Ming Peng, Shao-Bin Duan
Therapeutic Apheresis and Dialysis 2010, 14 (1): 27-34
20438517
Connective tissue growth factor (CTGF), a downstream mediator of transforming growth factor-beta1 (TGF-beta1) inducing fibrosis, has recently been implicated in peritoneal fibrosis. Extracellular matrix (ECM) accumulation and angiogenesis are characteristic changes in peritoneal fibrosis. In this study we investigated the effect of CTGF knockdown via interference RNA (RNAi) on ECM production and vascular endothelial growth factor (VEGF) expression induced by TGF-beta1 in human peritoneal mesothelial cells (HPMCs). Four CTGF short hairpin RNA (shRNA) expression constructs were generated using the pRetroSuper vector, and infectious retroviral particles were prepared to infect HPMCs. Expression levels of CTGF, fibronectin(FN), collagen 1 (col 1), laminin, and VEGF mRNA and protein were measured by semi-quantitative reverse transcription polymerase chain reaction and western blot assay. CTGF expression was increased after stimulation with TGF-beta1, but inhibited using each of the four independent CTGF shRNA constructs (P < 0.01). Moreover, expression of ECM proteins (FN, col 1, and laminin) and VEGF were upregulated after incubation with TGF-beta1, but elevated levels of ECM and VEGF induced by TGF-beta1 were significantly inhibited by RNAi (P < 0.01), but not by the empty retroviral vector (P > 0.05). From these results, we concluded that retrovirus-mediated CTGF shRNA can effectively inhibit ECM production and VEGF expression induced by TGF-beta1 in HPMCs. This study suggests that downregulation of CTGF may represent a potential therapeutic approach for peritoneal fibrosis through decreasing ECM accumulation and angiogenesis.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
20438517
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"