Connection between glucose metabolism and gene expression of critical neuromuscular components in Pompe's disease: new hints explaining the hypotonic phenotype?

Research output: Unpublished contribution to conferencePoster

Abstract

P80 - Connection between glucose metabolism and gene expression of critical neuromuscular components in Pompe's disease: new hints explainig the hypotonic phenotye? Laura DT Vo Ngoc1, Randy Osei1, Katrin Dohr2, Karen Sermon3, Sara Seneca1 & Alexander Gheldof1 1 Center of Medical Genetics, UZBrussel 2 Department of Paediatrics and Adolescent Medicine Graz, Austria 3 Reproduction and Genetics Unit, Vrije Universiteit Brussel (VUB) Pompe's disease is caused by the presence of bi-allelic pathogenic alterations in the GAA gene, resulting in the inability of patients to degrade glycogen. This translates to a hypotonic phenotype in combination with hypertrophic cardiomyopathy in severe cases. We performed genome wide mRNAseq on fibroblasts of Pompe patients and observed a marked increase of the transcription factor PPARgamma, together with an mRNA decrease of the neuromuscular junction component COL13A1 and the neuronally expressed KCNMA1 potassium ion channel. We have treated patients fibroblasts with the PPARgamma inhibitor G3335 and could observe a significant upregulation of both COL13A1 and KCNMA1 mRNA, indicating that PPARgamma functionality indeed impacts on expression of both genes. However, we could only show this effect in a subset of patients. As PPARgamma is a known important regulator of the energy metabolism and glucose is the buidling block of glycogen, we speculated that altering the glucose content of the culture medium could potentially impact on the expression of COL13A1 and KCNMA1 as well. Growing Pompe fibroblasts in glucose free medium indeed resulted in a significant mRNA upregulation of COL13A1 and KCNMA1 mRNA respectively. This is a important new finding which directly links the cellular glucose metabolism or uptake to the expression of two important mediators of neuromuscular junction and neuronal functionality. Furthermore, this finding could imply that a treatment regime of Pompe patients with a glucose restricted diet could be beneficial.
Original languageEnglish
Publication statusUnpublished - Feb 2022
Event22nd annual joint meeting BeSHG & NVHG: genetics retreat -
Duration: 20 Apr 202222 Apr 2022
https://beshg.be/index.php/meeting

Conference

Conference22nd annual joint meeting BeSHG & NVHG
Period20/04/2222/04/22
Internet address

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