ABSTRACT
AIM:To observe the effect of Yiqi Huayu Huatan decoction(YHHD)on unilaterral ureteral ob-struction(UUO)-induced renal interstitial fibrosis in rats, and to investigate the possible mechanism.METHODS: Fe-male SD rats(n=48)were randomly divided into sham group, model group, telmisartan group, and low-, middle-and high-dose YHHD groups,with 8 rats in each group.The UUO model rats was established by ligating left ureter.The rats in sham group and model group were treated with equal volume of normal saline, others were treated with the corresponding drugs daily.After 12 weeks,the rats were sacrificed.The serum samples were collected for determining the concentrations of cystatin C(Cys-C)and uric acid(UA).The morphological changes of the renal tissue were observed by PAS staining. The collagen fiber was observed by Masson staining.The mRNA expression of Krüppel-like factor 15(KLF15),high-mo-bility group box protein 1(HMGB1),nuclear factor-κB(NF-κB),IκB,monocyte chemotactic protein-1(MCP-1),inter-leukin-1β(IL-1β), tumor necrosis factor-α(TNF-α),fibronectin(FN),collagen type I(Col I)and Col-Ⅳwas detec-ted by real-time PCR.The protein expression of KLF15, HMGB1 and NF-κB was detected by Western blot.The protein expression of MCP-1 was determined by the method of immunohistochemistry.RESULTS:Compared with sham group,the deposition rate of collagen fibers and the concentration of Cys-C in model group were significantly increased(P<0.05), the mRNA and protein expression of KLF15 was significantly down-regulated(P<0.05), while the mRNA expression of HMGB1,NF-κB,IκB,MCP-1,IL-1β,TNF-α,FN,Col I and Col Ⅳand the protein expression of HMGB1,NF-κB and MCP-1 were significantly up-regulated(P<0.05).Compared with model group,the deposition rates of collagen fibers in middle-and high-dose YHHD groups and telmisartan group were significantly decreased(P<0.05),with down-regulated protein expression of HMGB1 and NF-κB and mRNA expression of IL-1βand TNF-α(P<0.05).The protein expression of KLF15 was significantly up-regulated in high-dose YHHD group and telmisartan group(P<0.05),while the protein ex-pression of MCP-1 and the mRNA expression of FN were significantly down-regulated(P<0.05).The mRNA expression of KLF15 was significantly up-regulated in high-dose YHHD group(P<0.05), while the mRNA expression of MCP-1, Col I and Col IV was significantly down-regulated(P<0.05).The mRNA expression of NF-κB and IκB was significantly down-regulated and the concentration of Cys-C was significantly decreased in each dose of YHHD groups and telmisartan group(P<0.05).No significant difference of UA level among the groups was observed.CONCLUSION:YHHD allevi-ates renal interstitial fibrosis in a dose-dependent manner, and YHHD at high dose shows the most obvious effect.The mechanism may be associated with the up-regulation of KLF15 and the down-regulation of HMGB1, NF-κB and its down-stream inflammation-related factors in the renal tissue.
ABSTRACT
AIM: To explore the clinical significance of Krüpple-like factor 15 (KLF15) protein expression in the patients with lung adenocarcinoma for exploring the therapeutic and prognositic biomarkers of lung cancer.ME-THODS: Four cases of lung adenocarcinoma tissues and matched adjacent tissues were collected from our hospital, and the expression of KLF15 protein in these tissues was analyzed by Western blot.At the same time, 72 cases of archived paraffin-embedded samples and clinical data of the patients with lung adenocarcinoma were also collected.The KLF15 protein expression in the archived paraffin-embedded lung adenocarcinoma samples was detected by immunohistochemical staining.The correlations between KLF15 protein expression and clinical characteristics of the patients including prognosis were also analyzed.In addition, the KLF15 protein was up-regulated in A549 cells, and then the effects of KLF15 protein on the viability of the cells were measured by CCK-8 assay.RESULTS: The protein expression of KLF15 in the 4 cases of lung adenocarcinoma tissues was significantly lower than that in matched paracancerous tissues.Fifty-three cases of lung adenocarcinoma specimens showed low expression or no expression of KLF15 protein in total 72 cases (73.6%).The 5-year survival rate of the patients with high expression of KLF15 protein in their specimens was higher than that of the patients with the low expression of KLF15 protein (P<0.01), and the expression of KLF15 protein was significantly correlated with the pathological staging (P<0.01) and T stage (P<0.01) of the patients with lung adenocarcinoma.Furthermore, the low expression of KLF15 protein was an important poor prognostic indicator of the patients.Up-regulation of KLF15 protein in the A549 cells significantly inhibited the growth of the cells.CONCLUSION: KLF15 inhibits the growth of lung adenocarcinoma cells.It could be used as a therapeutic target and a prognostic biomarker for the patients with lung adenocarcinoma.
ABSTRACT
Objective Based on animal model of left ventricular pressure overload induced cardiac fibrosis,to investigate the specific role and molecular mechanism of KLF15 gene in this process.Methods To establish rat animal model of pressure overload induced cardiac hypertrophy by aortic coarctation under non artificial ventilation conditions,and then release the constriction,to observe the rat heart color Doppler images,myocardial interstitial fibrosis features and protein expression level changes of KLF15、Transforming growth factor-β (TGF-β) 、Connective tissue growth factor (CTGF)、Myocardin-related transcription factor A(MRTF-A) in overload-unload corresponding time points.Results We successfully completed aortic banding and debanding operations by use of SD rats without artificial ventilation.Through color Doppler echocardiography detection,from images to know:the effect of constriction and loosening is definite.The expression of collagen type Ⅰ,collagen type Ⅲ,TGF-β,CTGF,MRTF-A were significantly higher and myocardial hypertrophy was aggravated but the KLF15 protein expression level was significantly lower in pressure overloaded rats than in Sham rats(all P ＜ 0.05).All values were in an increasing tendency with the constrictive time prolonged (P ＜ 0.05).The response to unloading was opposite,the sooner to loose the better to the recovery to normal.The differences of indicators are very notable (P ＜ 0.05).Conclusion By feedback regulation TGF-β,KLF15 inhibited the effect of CTGF and MRTF-A,reducing myocardial interstitial fibrosis.