PMID- 23508111 OWN - NLM STAT- MEDLINE DCOM- 20130722 LR - 20220309 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 33 IP - 11 DP - 2013 Jun TI - Brain-derived neurotrophic factor induces matrix metalloproteinase 9 expression in neurons via the serum response factor/c-Fos pathway. PG - 2149-62 LID - 10.1128/MCB.00008-13 [doi] AB - Brain-derived neurotrophic factor (BDNF) plays a pivotal role in the regulation of the transcription of genes that encode proplasticity proteins. In the present study, we provide evidence that stimulation of rat primary cortical neurons with BDNF upregulates matrix metalloproteinase 9 (MMP-9) mRNA and protein levels and increases enzymatic activity. The BDNF-induced MMP-9 transcription was dependent on extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and c-Fos expression. Overexpression of AP-1 dimers in neurons led to MMP-9 promoter activation, with the most potent being those that contained c-Fos, whereas knockdown of endogenous c-Fos by small hairpin RNA (shRNA) reduced BDNF-mediated MMP-9 transcription. Additionally, mutation of the proximal AP-1 binding site in the MMP-9 promoter inhibited the activation of MMP-9 transcription. BDNF stimulation of neurons induced binding of endogenous c-Fos to the proximal MMP-9 promoter region. Furthermore, as the c-Fos gene is a known target of serum response factor (SRF), we investigated whether SRF contributes to MMP-9 transcription. Inhibition of SRF and its cofactors by either overexpression of dominant negative mutants or shRNA decreased MMP-9 promoter activation. In contrast, MMP-9 transcription was not dependent on CREB activity. Finally, we showed that neuronal activity stimulates MMP-9 transcription in a tyrosine kinase receptor B (TrkB)-dependent manner. FAU - Kuzniewska, Bozena AU - Kuzniewska B AD - Department of Molecular and Cellular Neurobiology, Polish Academy of Sciences, Warsaw, Poland. FAU - Rejmak, Emilia AU - Rejmak E FAU - Malik, Anna R AU - Malik AR FAU - Jaworski, Jacek AU - Jaworski J FAU - Kaczmarek, Leszek AU - Kaczmarek L FAU - Kalita, Katarzyna AU - Kalita K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130318 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (RNA, Small Interfering) RN - 0 (Serum Response Factor) RN - 0 (Transcription Factor AP-1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - Y37615DVKC (Bicuculline) SB - IM MH - Animals MH - Base Sequence MH - Bicuculline/pharmacology MH - Binding Sites MH - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology MH - Cells, Cultured MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Gene Expression Regulation, Enzymologic MH - Matrix Metalloproteinase 9/*genetics/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Molecular Sequence Data MH - Neurons/drug effects/*physiology MH - Promoter Regions, Genetic MH - Proto-Oncogene Proteins c-fos/genetics/*metabolism MH - RNA, Small Interfering/genetics MH - Rats MH - Rats, Wistar MH - Serum Response Factor/*metabolism MH - Transcription Factor AP-1/genetics/metabolism PMC - PMC3648073 EDAT- 2013/03/20 06:00 MHDA- 2013/07/23 06:00 PMCR- 2013/12/01 CRDT- 2013/03/20 06:00 PHST- 2013/03/20 06:00 [entrez] PHST- 2013/03/20 06:00 [pubmed] PHST- 2013/07/23 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - MCB.00008-13 [pii] AID - 00008-13 [pii] AID - 10.1128/MCB.00008-13 [doi] PST - ppublish SO - Mol Cell Biol. 2013 Jun;33(11):2149-62. doi: 10.1128/MCB.00008-13. Epub 2013 Mar 18.