Journal article
The PPAR-γ Agonist Pioglitazone Modulates Proliferation and Migration in HUVEC, HAOSMC and Human Arteriovenous Fistula-Derived Cells
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v 24(5), 4424
Mar 2023
PMID: 36901853
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The failure of arteriovenous fistulas (AVFs) following intimal hyperplasia (IH) increases morbidity and mortality rates in patients undergoing hemodialysis for chronic kidney disease. The peroxisome-proliferator associated receptor (PPAR-gamma) may be a therapeutic target in IH regulation. In the present study, we investigated PPAR-gamma expression and tested the effect of pioglitazone, a PPAR-gamma agonist, in different cell types involved in IH. As cell models, we used Human Endothelial Umbilical Vein Cells (HUVEC), Human Aortic Smooth Muscle Cells (HAOSMC), and AVF cells (AVFCs) isolated from (i) normal veins collected at the first AVF establishment (T0), and (ii) failed AVF with IH (T1). PPAR-gamma was downregulated in AVF T1 tissues and cells, in comparison to T0 group. HUVEC, HAOSMC, and AVFC (T0 and T1) proliferation and migration were analyzed after pioglitazone administration, alone or in combination with the PPAR-gamma inhibitor, GW9662. Pioglitazone negatively regulated HUVEC and HAOSMC proliferation and migration. The effect was antagonized by GW9662. These data were confirmed in AVFCs T1, where pioglitazone induced PPAR-gamma expression and downregulated the invasive genes SLUG, MMP-9, and VIMENTIN. In summary, PPAR-gamma modulation may represent a promising strategy to reduce the AVF failure risk by modulating cell proliferation and migration.
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Details
- Title
- The PPAR-γ Agonist Pioglitazone Modulates Proliferation and Migration in HUVEC, HAOSMC and Human Arteriovenous Fistula-Derived Cells
- Publication Details
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v 24(5), 4424
- Publisher
- MDPI; BASEL
- Grant note
- This research was funded in part through RFO institutional funding and by Fondazione Cassa di Risparmio di Imola for the project: 7426.0320-2020.0246-Role of the microRNA in the intimal hyperplasia process in the arteriovenous fistulae, for the acquisition of the HAOSMC cell model.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000948166700001
- Scopus ID
- 2-s2.0-85149976854
- Other Identifier
- 991021861205304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary