Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neurons

Version 1 : Received: 29 September 2023 / Approved: 30 September 2023 / Online: 30 September 2023 (07:16:03 CEST)

A peer-reviewed article of this Preprint also exists.

Pabian-Jewuła, S.; Ambrożek-Latecka, M.; Brągiel-Pieczonka, A.; Nowicka, K.; Rylski, M. Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neuron-like Cells. Genes 2023, 14, 2028. Pabian-Jewuła, S.; Ambrożek-Latecka, M.; Brągiel-Pieczonka, A.; Nowicka, K.; Rylski, M. Identification of Molecular Mechanisms Responsible for the MMP-9-1562C/T Dependent Differential Regulation of Matrix Metalloproteinase-9 Expression in Human Neuron-like Cells. Genes 2023, 14, 2028.

Abstract

The MMP-9-1562C/T polymorphism influence incidence and course of many diseases of the central nervous system. We found, using luciferase assays and Q-RT-PCR technique, allele-specific in-fluence of MMP-9-1562C/T polymorphism on the MMP-9 promoter activity and on the expression of MMP-9 mRNA in human neurons derived from SH-SY5Y cells. Then, we have elucidated the mechanism responsible for the allele-specific action of the MMP-9-1562C/T polymorphism on transcriptional regulation of the MMP-9 gene using pull-down assay combined with mass spec-trometry analysis, EMSA and EMSA supershift techniques, as well as DsiRNA-dependent gene silencing. We have found that MMP-9 promoter activity and MMP-9 mRNA expression are reg-ulated in human neurons in the MMP-9-1562C/T allele-specific manner with stronger upregulation conferred by the C allele. Moreover, we have revealed that the allele-specific action of the MMP-9-1562C/T polymorphism on the neuronal MMP-9 expression is related to HDAC1 and ZNF384 transcriptional regulators. We show that HDAC1 and ZNF384 bind differentially to the C and the T alleles forming in vitro different regulatory complexes. Moreover, our data demonstrate that HDAC1 and ZNF384 downregulate differentially the MMP-9 gene promoter activity and MMP-9 mRNA expression in vivo in human neurons acting mostly via the T allele.

Keywords

MMP-9; MMP-9-1562C/T polymorphism; transcriptional regulation; brain; human neurons

Subject

Biology and Life Sciences, Neuroscience and Neurology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.