Expression changes of GZMA, GZMB, TSP-1, TLR and IL-1 five cell apoptosis pathways related genes in liver regeneration

doi:10.16098/j.issn.0529-1356.2016.04.022

Abstract

Abstract:

Objective To investigate the expression changes of five cell apoptosis pathway genes, granzyme A (GZMA), granzyme B (GZMB), thrombospondin-1 (TSP-1), Toll-like receptors (TLR) and interleukin-1 (IL-1), in the process of regeneration liver (LR). Methods Rats were randomly divided into 33 groups with 6 rats in each group. Genome Rat 230 2.0 was used to detect the expression of genes in four cell apoptosis pathways in rats after partial hepatectomy (PH). Real-time PCR and Western blotting technology were used to verify the results of the chip, and the expression changes of apoptosis pathway genes in liver regeneration were analyzed by bioinformatics methods. Results Both Real-time PCR and Western blotting were in agreement with the test results of Genome Rat 230 2.0 chip; 9, 8, 24, 31 and 34 genes were associated with liver regeneration in the four cell apoptosis pathways.They were mainly expressed at the start stage of liver regeneration. The maximum number of expressed genes were in cell proliferation phase. The similarity of their expression was totally up regulation, up regulation advantage, totally down regulation, down regulation advantage, up regulation equal to down regulation of 5 categories. The expression of most genes in liver regeneration was enhanced, and the expression of few gene was decreased. Time correlation was divided into 13 groups. Analysis of the role of apoptosis pathway related genes in liver regeneration by using the gene synergy model (Et), GZMA pathway promoted apoptosis in the late stage of liver regeneration; TLR pathway promotes cell apoptosis almost in the whole liver regeneration; GZMB, TSP-1 and IL-1 pathways did not play the role of apoptosis in liver regeneration. Conclusion Two apoptosis pathways, GZMA and TSP-1, regulate apoptosis in liver regeneration.

Key words: Rat Genome 230 2.0 chip, Partial hepatectomy, Liver regeneration, Real-time PCR, Western blotting, Rat

XING Xue-kun LIU Zhen-hua LI Meng-hua XU Cun-shuan*. Expression changes of GZMA, GZMB, TSP-1, TLR and IL-1 five cell apoptosis pathways related genes in liver regeneration[J]. AAS, 2016, 47(4): 563-571.

References

［1］Jiang WW, Hao XX, Guo YQ, et al. Caspase signaling pathway regulates hepatocyte apoptosis in rat liver regeneration ［J］. Acta Anatomica Sinica, 2012, 43(3): 359-365. (in Chinese)
蒋文文, 郝晓霞, 郭雅琼, 等. Caspase信号通路调控大鼠再生肝肝细胞的凋亡［J］. 解剖学报, 2012, 43(3): 359-365.
［2］Shen YH, Lu Q, Yang YJ, et al. JNK signaling pathway regulates proliferation and apoptosis of eight liver cell types during rat liver regeneration ［J］. Acta Anatomica Sinica, 2012, 43(2): 189-197. (in Chinese)
申亚慧, 陆琼, 杨彦杰, 等. JNK信号通路调控大鼠再生肝8种细胞的增殖和凋亡［J］. 解剖学报, 2012, 43(2): 189-197.
［3］Lu F, Lamontagne J, Sun A, et al. Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis ［J］. Immunology, 2011, 134(4): 398-408.
［4］Jacquemin G, Margiotta D, Kasahara A, et al. Granzyme B-induced mitochondrial ROS are required for apoptosis ［J］. Cell Death Differ, 2015, 22(5): 862-874.
［5］El Btaouri H, Morjani H, Greffe Y, et al. Role of JNK/ATF-2 pathway in inhibition of thrombospondin-1 (TSP-1) expression and apoptosis mediated by doxorubicin and camptothecin in FTC-133 cells ［J］. Biochim Biophys Acta, 2011, 1813(5): 695-703.
［6］Panneerselvam P, Ding JL. Beyond TLR signaling-the role of SARM in antiviral immune defense, apoptosis & development ［J］. Int Rev Immunol, 2015, 34(5): 432-444.
［7］Yang B, Elias JE, Bloxham M, et al. Synthetic small interfering RNA down-regulates caspase-3 and affects apoptosis, IL-1 beta, and viability of porcine proximal tubular cells ［J］. J Cell Biochem, 2011, 112(5): 1337-1347.
［8］Xu C, Yang Y, Yang J, et al. Analysis of the role of the integrin signaling pathway in hepatocytes during rat liver regeneration ［J］. Cell Mol Biol Lett, 2012, 17(2): 274-288.
［9］Sakahira H, Enari M, Nagata S. Corrigendum: Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis ［J］. Nature, 2015, 526(7575): 728.
［10］Park JH, Lee SW, Yang SW, et al. Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in response to DNA damage ［J］. Nat Commun, 2014, 5: 5483.
［11］Du CP, Tan R, Hou XY. Fyn kinases play a critical role in neuronal apoptosis induced by oxygen and glucose deprivation or amyloid-beta peptide treatment ［J］. CNS Neurosci Ther, 2012, 18(9): 754-761.
［12］Williams ME, Lu X, McKenna WL, et al. UNC5A promotes neuronal apoptosis during spinal cord development independent of netrin-1 ［J］. Nat Neurosci, 2006, 9(8): 996-998.
［13］Andzinski L, Wu CF, Lienenklaus S, et al. Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN-beta ［J］. Int J Cancer, 2015, 136(3): 572-583.
［14］Smith MR, Jin F, Joshi I. Milatuzumab and veltuzumab induce apoptosis through JNK signalling in an NF-kappa B dependent human transformed follicular lymphoma cell line ［J］. Br J Haematol, 2014, 165(1): 151-153.
［15］Grenda DS, Murakami M, Ghatak J, et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis ［J］. Blood, 2007, 110(13): 4179-4187.
［16］Paul-Samojedny M, Pudelko A, Kowalczyk M, et al. Knockdown of AKT3 and PI3KCA by RNA interference changes the expression of the genes that are related to apoptosis and autophagy in T98G glioblastoma multiforme cells ［J］. Pharmacol Rep, 2015, 67(6): 1115-1123.
［17］Islam TC, Smith CI. The cellular phenotype conditions Btk for cell survival or apoptosis signaling ［J］. Immunol Rev, 2000, 178: 49-63.
［18］Zhou X, Li H, Chai Y, et al. Leptin inhibits the apoptosis of endometrial carcinoma cells through activation of the nuclear factor kB-inducing kinase/lkB kinase Pathway ［J］. Int J Gynecol Cancer, 2015, 25(5): 770-778.

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