C-Src/Jak2/PDGFR/PKCδ-dependent MMP-9 Induction is Required for Thrombin-stimulated Rat Brain Astrocytes Migration

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2013 Sep 11

PMID 24018979

Citations 16

Authors

Chih-Chung Lin

I-Ta Lee

Pei-Ling Chi

Hsi-Lung Hsieh

Shin-Ei Cheng

Li-Der Hsiao

Chiung-Ju Liu

Chuen-Mao Yang

Affiliations

Soon will be listed here.

Abstract

Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Thrombin has been known as a regulator of MMP-9 expression and cells migration. However, the mechanisms underlying thrombin-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) were not completely understood. Here, we demonstrated that thrombin induced the expression of pro-form MMP-9 in RBA-1 cells and cells migration which were attenuated by pretreatment with the inhibitor of receptor tyrosine kinase (Genistein), c-Src (PP1), Jak2 (AG490), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), PKCs (Ro318220), PKCδ (Rottlerin), or NF-κB (Bay11-7082) and transfection with siRNA of c-Src, PDGFR, Akt, PKCδ, ATF2, p65, IKKα, or IKKβ. In addition, thrombin-stimulated c-Src, Jak2, or PDGFR phosphorylation was inhibited by a thrombin inhibitor (PPACK), PP1, AG490, or AG1296. Thrombin further stimulated c-Src and PDGFR complex formation in RBA-1 cells. Thrombin also stimulated Akt and PKCδ phosphorylation and PKCδ translocation which were reduced by PPACK, PP1, AG490, AG1296, or LY294002. We further observed that thrombin markedly stimulated ATF2 or IκBα phosphorylation and NF-κB p65 translocation which were inhibited by Rottlerin or LY294002. Finally, thrombin stimulated in vivo binding of p65 to the MMP-9 promoter, which was reduced by pretreatment with Rottlerin or LY294002. These results concluded that in RBA-1 cells, thrombin activated a c-Src/Jak2/PDGFR/PI3K/Akt/PKCδ pathway, which in turn triggered ATF2 and NF-κB activation and ultimately induced MMP-9 expression associated with cell migration.

Citing Articles

The neuroprotection of hyperbaric oxygen therapy against traumatic brain injury via NF-κB/MAPKs-CXCL1 signaling pathways.

Xia A, Huang H, You W, Liu Y, Wu H, Liu S Exp Brain Res. 2021; 240(1):207-220.

PMID: 34687331 DOI: 10.1007/s00221-021-06249-8.

Galangin Inhibits LPS-Induced MMP-9 Expression via Suppressing Protein Kinase-Dependent AP-1 and FoxO1 Activation in Rat Brain Astrocytes.

Yang C, Hsiao L, Yang C J Inflamm Res. 2020; 13:945-960.

PMID: 33244253 PMC: 7685391. DOI: 10.2147/JIR.S276925.

Lipopolysaccharide-Induced Matrix Metalloproteinase-9 Expression Associated with Cell Migration in Rat Brain Astrocytes.

Yang C, Lin C, Hsiao L, Kuo J, Tseng H, Yang C Int J Mol Sci. 2020; 21(1).

PMID: 31905967 PMC: 6982104. DOI: 10.3390/ijms21010259.

Platelet-Derived Growth Factor Receptor-α and β are Involved in Fluid Shear Stress Regulated Cell Migration in Human Periodontal Ligament Cells.

Zheng L, Shi Q, Na J, Liu N, Guo Y, Fan Y Cell Mol Bioeng. 2019; 12(1):85-97.

PMID: 31719900 PMC: 6816651. DOI: 10.1007/s12195-018-0546-7.

Galangin Inhibits Thrombin-Induced MMP-9 Expression in SK-N-SH Cells via Protein Kinase-Dependent NF-κB Phosphorylation.

Yang C, Lin C, Hsiao L, Yang C Int J Mol Sci. 2018; 19(12).

PMID: 30562971 PMC: 6321481. DOI: 10.3390/ijms19124084.

References

Wang H, Hsieh H, Wu C, Yang C . Oxidized low-density lipoprotein-induced matrix metalloproteinase-9 expression via PKC-delta/p42/p44 MAPK/Elk-1 cascade in brain astrocytes. Neurotox Res. 2009; 17(1):50-65. DOI: 10.1007/s12640-009-9077-2. View

Debeir T, Gueugnon J, Vige X, Benavides J . Transduction mechanisms involved in thrombin receptor-induced nerve growth factor secretion and cell division in primary cultures of astrocytes. J Neurochem. 1996; 66(6):2320-8. DOI: 10.1046/j.1471-4159.1996.66062320.x. View

Wu C, Hsieh H, Sun C, Yang C . IL-1beta induces MMP-9 expression via a Ca2+-dependent CaMKII/JNK/c-JUN cascade in rat brain astrocytes. Glia. 2009; 57(16):1775-89. DOI: 10.1002/glia.20890. View

Moore C, Abdullah S, Brown A, Arulpragasam A, Crocker S . How factors secreted from astrocytes impact myelin repair. J Neurosci Res. 2010; 89(1):13-21. DOI: 10.1002/jnr.22482. View

Liu D, Ander B, Xu H, Shen Y, Kaur P, Deng W . Blood-brain barrier breakdown and repair by Src after thrombin-induced injury. Ann Neurol. 2010; 67(4):526-33. PMC: 2919346. DOI: 10.1002/ana.21924. View

Hsieh H, Wang H, Wu W, Chu P, Yang C . Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: roles of ROS-dependent ERK- and JNK-NF-κB pathways. J Neuroinflammation. 2010; 7:88. PMC: 3002339. DOI: 10.1186/1742-2094-7-88. View

Lee I, Wang S, Lee C, Chang C, Lin C, Luo S . Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells. J Immunol. 2008; 181(7):5098-110. DOI: 10.4049/jimmunol.181.7.5098. View

Lee C, Lin C, Lin W, Liang K, Luo S, Wu C . TNF-alpha induces MMP-9 expression via activation of Src/EGFR, PDGFR/PI3K/Akt cascade and promotion of NF-kappaB/p300 binding in human tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2006; 292(3):L799-812. DOI: 10.1152/ajplung.00311.2006. View

Yang C, Lin C, Lee I, Lin Y, Yang C, Chen W . Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes. J Neuroinflammation. 2012; 9:12. PMC: 3298505. DOI: 10.1186/1742-2094-9-12. View

10.

Ransohoff R, Brown M . Innate immunity in the central nervous system. J Clin Invest. 2012; 122(4):1164-71. PMC: 3314450. DOI: 10.1172/JCI58644. View

11.

Choi S, Lee D, Kim S, Jin B . Thrombin-induced oxidative stress contributes to the death of hippocampal neurons in vivo: role of microglial NADPH oxidase. J Neurosci. 2005; 25(16):4082-90. PMC: 6724962. DOI: 10.1523/JNEUROSCI.4306-04.2005. View

12.

Lee I, Lin C, Lee C, Hsieh P, Yang C . Protective effects of (-)-epigallocatechin-3-gallate against TNF-α-induced lung inflammation via ROS-dependent ICAM-1 inhibition. J Nutr Biochem. 2012; 24(1):124-36. DOI: 10.1016/j.jnutbio.2012.03.009. View

13.

Cui G, Gao X, Qi S, Gillani A, Gao L, Shen X . The action of thrombin in intracerebral hemorrhage induced brain damage is mediated via PKCα/PKCδ signaling. Brain Res. 2010; 1398:86-93. DOI: 10.1016/j.brainres.2010.11.095. View

14.

Reimold A, Grusby M, Kosaras B, FRIES J, Mori R, Maniwa S . Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature. 1996; 379(6562):262-5. DOI: 10.1038/379262a0. View

15.

Rosenberg G . Matrix metalloproteinases in neuroinflammation. Glia. 2002; 39(3):279-91. DOI: 10.1002/glia.10108. View

16.

Turgeon V, Lloyd E, Wang S, Festoff B, Houenou L . Thrombin perturbs neurite outgrowth and induces apoptotic cell death in enriched chick spinal motoneuron cultures through caspase activation. J Neurosci. 1998; 18(17):6882-91. PMC: 6792988. View

17.

Kim J, Lee J, Kim S, Choi Y, Lee W, Jeong M . Thrombin-induced Migration and Matrix Metalloproteinase-9 Expression Are Regulated by MAPK and PI3K Pathways in C6 Glioma Cells. Korean J Physiol Pharmacol. 2011; 15(4):211-6. PMC: 3186922. DOI: 10.4196/kjpp.2011.15.4.211. View

18.

Wang H, Hsieh H, Yang C . Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid. J Neuroinflammation. 2010; 7:84. PMC: 2997088. DOI: 10.1186/1742-2094-7-84. View

19.

Yang C, Lee I, Lin C, Yang Y, Luo S, Kou Y . Cigarette smoke extract induces COX-2 expression via a PKCalpha/c-Src/EGFR, PDGFR/PI3K/Akt/NF-kappaB pathway and p300 in tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009; 297(5):L892-902. DOI: 10.1152/ajplung.00151.2009. View

20.

Lee I, Shih R, Lin C, Chen J, Yang C . Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Commun Signal. 2012; 10(1):33. PMC: 3509033. DOI: 10.1186/1478-811X-10-33. View