[SREBP-1c knockdown attenuated fatty degeneration in hepatic L02 cells and inhibited CCL2 and FGF21 protein expression].

Autor:	Wang WD; Department of Gastroenterology, Daping Hospital and Institute of Field Surgery Research, Third Military Medical University, Chongqing 400042, China., Wang J, Fan LL, Xiong J, Sun WJ, Hu L, Yang L, Chen DF
Jazyk:	čínština
Zdroj:	Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology [Zhonghua Gan Zang Bing Za Zhi] 2011 Sep; Vol. 19 (9), pp. 664-9.
DOI:	10.3760/cma.j.issn.1007-3418.2011.09.008
Abstrakt:	Objective: To study the effect of SREBP-1c silencing on lipid metabolism and expression of inflammatory chemokines in a NAFLD model with endoplasmic reticulum stress. Method: NAFLD model was established in L02 cells treated with oleic acid. SREBP-1c expression was inhibited using RNA interference with a p Silencer-1.0-U6-4476 vector. After transfection with p Silencer-1.0-U6-4476 or control vector for 0 h, 24 h, 48 h and 72 h, the extent of fatty degeneration was shown by Oil Red O staining. The mRNA and protein expression of inflammatory chemokine CCL2 and basic fibroblast growth factor-21 (FGF21) were determined by real time PCR and Western blot respectively. Results: SREBP-1c silenced L02 cells showed fat droplets with smaller diameter and attenuated fatty deposition, as compared with control cells. The relative CCL2 mRNA levels in SREBP-1c silencing vector transfected L02 cells were 1.03+/-0.11 for 0 h, 1.11+/-0.21 for 24 h, 0.88+/-0.16 for 48 h, and 1.05+/-0.15 for 72 h, which showed no significant difference as compared with control cells (P>0.05, respectively). In addition, no difference was found between the different time points within the same group (P>0.05). However, CCL2 protein levels in SREBP-1c silenced cells were 1.19+/-0.15, 1.07+/-0.18, 0.48+/-0.14, and 0.05+/-0.24 after transfection for 0 h, 24 h, 48 h, and 72 h respectively, which were significantly downregulated as compared to the control group (P<0.01). And CCL2 protein levels between different time points in SREBP-1c silenced cells were also distinct (P<0.01). The relative FGF21 mRNA levels in SREBP-1c silenced L-02 cells were 1.01+/-0.08, 0.91+/-0.22, 0.98+/-0.20, and 1.02+/-0.12 for 0 h, 24 h, 48 h, and 72 h respectively, which were not statistically different as compared with the corresponding control cells. Statistic difference of FGF21 mRNA levels in SREBP-1c knockdown cells of different time points was not found (P>0.05). In striking contrast, robust down regulation of FGF21 protein in SREBP-1c silenced cells was observed, with 0.81+/-0.05, 0.66+/-0.12, 0.58+/-0.08 and 0.19+/-0.13 after transfection for 0 h, 24 h, 48 h and 72 h respectively, as compared to control group (P<0.01). And differences in FGF21 protein level between different time points in SREBP-1c silenced cells were also demonstrated (P<0.01). Conclusion: SREBP-1c knockdown attenuated fatty deposition in oleic acid treated L02 cells. In addition, silencing of SREBP-1c expression reduced expressions of CCL2 and FGF21 proteins posttranscriptionally, which may play a role in endoplasmic reticulum stress induced inflammatory response in NAFLD.
Databáze:	MEDLINE
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