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Inhibitory effect of receptor for advanced glycation end product-specific small interfering RNAs on the development of hepatic fibrosis in primary rat hepatic stellate cells
- Source :
- Molecular Medicine Reports. 12:569-574
- Publication Year :
- 2012
- Publisher :
- Spandidos Publications, 2012.
-
Abstract
- Specific small interfering RNAs (siRNAs) targeting receptor for advanced glycation end products (RAGE) inhibit the expression of RAGE, α-smooth muscle actin and type I collagen in the T6 hepatic stellate cells (HSCs), indicating that RAGE is important for the activation of HSCs and the expression of collagen. The present study aimed to investigate the effect of specific siRNAs targeting RAGE on the development of hepatic fibrosis (HF), using primary rat HSCs, which were isolated and cultured in vitro. The expression vectors for specific siRNAs targeting RAGE were constructed and transfected into primary rat HSCs. Untreated and nonspecific siRNA-transfected primary rat HSCs served as controls. The expression levels of RAGE, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), laminin (LN), hyaluronic acid (HA) and N-terminal procollagen III propeptide (PIIINP) in primary HSCs were detected by reverse transcription quantitative polymerase chain reaction and western blotting. The mRNA and 42 kD protein expression of RAGE in the pAKD-GR126-transfected primary HSCs were significantly downregulated compared with those in the untreated and the pAKD-negative control (NC)-transfected controls. The mRNA and protein expression levels of IL-6, TNF-α, TGF-β1, CTGF, LN, HA and PIIINP in the pAKD-GR126-transfected primary HSCs were also markedly downregulated compared with those in the untreated and pAKD-NC-transfected controls. Therefore, RAGE-specific siRNAs inhibited the expression of RAGE in primary rat HSCs and inhibited the development of HF.
- Subjects :
- Liver Cirrhosis
Cancer Research
Small interfering RNA
medicine.medical_treatment
Receptor for Advanced Glycation End Products
Biology
Biochemistry
Collagen Type I
RAGE (receptor)
chemistry.chemical_compound
Hepatic Stellate Cells
Genetics
medicine
Animals
Humans
RNA, Messenger
RNA, Small Interfering
Molecular Biology
Messenger RNA
Growth factor
Molecular biology
Actins
Rats
CTGF
Disease Models, Animal
Gene Expression Regulation
Liver
Oncology
chemistry
Hepatic stellate cell
Molecular Medicine
Advanced glycation end-product
Type I collagen
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....79b0783b7f9b448d114f87e64e46caa0