ABSTRACT
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is an endogenous short peptide produced through the continuous hydrolysis of Thymosin β4 by meprin-α and prolyl oligopeptidase. It has the functions of immune regulation, promoting angiogenesis, tumorigenesis and anti-fibrosis in organs. In this paper, according to some our research results and related literatures in recent years, a review of Ac-SDKP research progress was written.
Subject(s)
Humans , Oligopeptides , Cell Transformation, NeoplasticABSTRACT
Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.
Subject(s)
Animals , Rats , HSP27 Heat-Shock Proteins , Oligopeptides , Rats, Wistar , Silicon Dioxide , Silicosis/metabolismABSTRACT
Objective: To explore whether N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits the formation of silica nodules and the deposition of collagen by inhibiting the expressions of inflammatory factor myeloid-related protein14 (MRP-14) and collagen in silicosis rats. Methods:The silicosis model of rats was established by one-off bronchial instillation of silicon (SiO2) dust. Sixty healthy adult rats of SPF grade were randomly divided into six groups: control 4-week group, control 8-week group, silicosis model 4-week group, silicosis model 8-week group, Ac-SDKP prevention treatment group, and Ac-SDKP anti-fibrosis treatment group, with ten rats in each group. Immunohistochemical method was used to detect the expression of MRP-14 protein in silicosis model tissues. Western blot method was used to detect the expressions of MRP-14 and collagen protein in silicosis model tissues. Results: Compared with those in the corresponding control group, the expressions of MRP-14 and collagen in silicosis fibrosis areas were significantly increased in the dust-exposed group (P<0.05). Compared with those in the silicosis model 8-week group, the expressions of MRP-14 and collagen were significantly decreased after Ac-SDKP intervention (P<0.05). Conclusion: Ac-SDKP can inhibit silicosis in rats by inhibiting the regulation of MRP-14 expression.
ABSTRACT
Objective To study the effects of N-acetyl-seryl-aspartyl-lysyl-proline(AcSDKP) on proliferation and synthesis and secretion of extracellular matrix(ECM) in rat active hepatic stellate cells(HSCs). Methods Primary cultures of HSCs when actived were subjected to AcSDKP(0.01, 0.1, 1, 10 and 100 nmol/L, respectively) treatment, and control group was established. The expression of collagen Ⅰ(ColⅠ) and collagen Ⅲ(Col Ⅲ) mRNA were analyzed with RT-PCR. The proliferation of HSCs was detected by MTT. Hyaluronic acid (HA) and laminin(LN) in the supernatant were determined by enzyme-linked immunosorbent assay. Results Compared with control group, the proliferation of active HSCs was significantly inhibited by 1 and 10 nmol/L AcSDKP. 1, 10 nmol/L AcSDKP and 0.1 to 100 nmol/L AcSDKP significantly inhibited the expression of HSCs ColⅠ mRNA and Col Ⅲ mRNA, respectively. Expression of HA and LN in the supernatant were significantly inhibited by 0.1, 1, 10 nmol/L and 0.1, 1 nmol/L AcSDKP, respectively. ConclusionAcSDKP can inhibit synthesis and secretion of ECM in active HSCs in a dose-dependent manner, with a maximum inhibition effect at 1 nmol/L AcSDKP. The mechanism may involve the inhibition of the proliferation of HSCs,which leads to the decrease of HSCs that synthesize and secrete ECM.