geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Effect of small interfering RNA on the expression of connective tissue growth factor and type I and III collagen in skin fibroblasts of patients with systemic sclerosis


, : Effect of small interfering RNA on the expression of connective tissue growth factor and type I and III collagen in skin fibroblasts of patients with systemic sclerosis. British Journal of Dermatology 155(6): 1145-1153

Background Systemic sclerosis (SSc) is characterized by an excessive production of extracellular matrix. It is widely accepted that fibrosis is induced by transforming growth factor (TGF)-beta in the early stage and is subsequently maintained by connective tissue growth factor (CTGF). CTGF is a cysteine-rich mitogenic peptide that has been involved in various fibrotic disorders and can be induced in fibroblasts by activation with TGF-beta.Objectives To evaluate the effect of small interfering RNA (siRNA) targeting CTGF on the expression of CTGF and type 1 and type III collagen in SSc.Methods Skin fibroblasts from patients with SSc were cultured in vitro and later transfected using four CTGF-specific siRNAs and one nonspecific siRNA. The effect of CTGF-specific siRNAs on the expression of CTGF and type I and type Ill collagen was examined and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunocytochemistry.Results Semiquantitative RT-PCR analysis showed that the four CTGF-specific siRNAs significantly reduced CTGF mRNA expression (P < 0.001), of which siRNA742 showed the strongest inhibitory effect with an inhibitory rate of 73%. Three of the four siRNAs could also depress the transcriptional levels of type I and type III collagen mRNA (P < 0.001), of which siRNA742 showed the strongest inhibitory effect with an inhibitory rate of 37% and 29% for type I and type Ill collagen, respectively. Western blot analysis further demonstrated that three CTGF-specific siRNAs could significantly decrease CTGF protein level (P < 0.001). In addition, immunocytochemical analysis showed that the expression of type I collagen was significantly decreased in fibroblasts after transfection with siRNA742, whereas inhibition of expression of type III collagen was modest.Conclusions Our data for the first time showed that CTGF RNA interference could inhibit expression of CTGF and type I and III collagen in SSc fibroblasts and indicated that CTGF might be an upstream factor regulating type I and type Ill collagen synthesis, particularly type 1 collagen. Our findings suggest that silencing CTGF expression might facilitate a potential therapeutic approach for SSc.

US$19.90

PMID: 17107381

DOI: 10.1111/j.1365-2133.2006.07438.x


Other references

Havrilla, G.J.; Green, R.B.; Trask, T.O., 1978: Capacitor modification for the Schenck-Metcalf nitrogen laser. Applied Optics 17(22): 3525-3527

Sanchez Crespo M.; Weber K.H., 1988: Web 2086. Drugs of the Future 13(3): 242-246

Harmony J.A.K., 1981: Inhibition of phosphatidyl inositol turnover in mitogen activated lymphocytes by apo protein e. Federation Proceedings: 1634

Player, S.; Godden, S.; Pollock, A., 2000: Private finance initiative. Well-laid plans. Private finance schemes in primary care will not be subject to the controls required in hospital programmes. Insurance companies are interested in partnerships with primary care in order to influence NHS spending as services are increasingly contr...

Jirasek, Jan E., 1965: The histogenesis and histochemistry of the beta cells in the islands of Langerhans in the pancreas of human embryos. In 20 human fetuses fixed in Romeis' solution the histogenesis of beta cells in Langerhans' islands was investigated by means of aldehyde fuchsin staining and disulfide group eduction by DDD, according to Barrnett and collaborators[long...

McConnell, M.E., 1990: Echocardiography in classical tetralogy of Fallot. Seminars in Thoracic and Cardiovascular Surgery 2(1): 2-11

Baldo, G.; Mayer, F.Quoos.; Martinelli, B.; Dilda, A.; Meyer, F.; Ponder, K.P.; Giugliani, R.; Matte, U., 2012: Evidence of a progressive motor dysfunction in Mucopolysaccharidosis type I mice. Mucopolysaccharidosis (MPS) type I (Hurler syndrome) is a lysosomal storage disorder characterized by deficiency of alpha-<small-caps>l</small-caps>-iduronidase (IDUA), intracellular storage of glycosaminoglycans (GAGs) and progressive...

FanBaoMin; ChenQinJuan; GuoXinBao; Pauleit,S.; LiuLi; XieBaoYuan, 2008: A case study report for Urban Forestry Policy Project Co-funded by EC analysis of urban forestry policy in Hangzhou, China. Hangzhou is a typical city on the establishment of urban forest in Zhejiang, China, so it was identified as a case study site in Urban Forestry Policy Project Co-funded by EC. The name of the project is "Developing Policy Formulation and Impl...

Bignon, J.S.; Aron, Y.; Ju, L.Y.; Kopferschmitt, M.C.; Garnier, R.; Mapp, C.; Fabbri, L.M.; Pauli, G.; Lockhart, A.; Charron, D., 1994: HLA class II alleles in isocyanate-induced asthma. Studying genetic factors that control human immune responsiveness may further our understanding of specific types of asthma in which the role of immune factors is uncertain to date. HLA Class II gene products are involved in the control of immune...

Ekstein, R., 1955: Vicissitudes of the internal image in the recovery of a borderline schizophrenic adolescent. Bulletin of the Menninger Clinic 19(3): 86-92