Rare and intractable fibrodysplasia ossificans progressiva shows different PBMC phenotype possibly modulated by ascorbic acid and propranolol treatment.

Autor:	Nascimento DR; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Balaniuc SLB; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Palhares DB; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Underwood A; Walsh University, Division of Mathematics and Sciences, North Canton, OH, USA., Palhares MG; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Alves F; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil.; Centro Universitário Metodista Izabela Hendrix- IMIH, Belo Horizonte, MG, Brazil., Vieira FO; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil.; Centro Universitário Metodista Izabela Hendrix- IMIH, Belo Horizonte, MG, Brazil., Souza-Fagundes EM; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil., Giuliani LR; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Xavier PCN; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Puerto HLD; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil., Santos RAS; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil., Milsted A; Walsh University, Division of Mathematics and Sciences, North Canton, OH, USA., Brum JM; Procter & Gamble Health Care & Global Clinical Sciences, Mason, OH, USA., Silva IS; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil., Martins AS; UFMS/ Faculty of Medicine, Campo Grande, MS, Brazil.; UFMG/ Department of Physiology and Biophysics, Belo Horizonte, MG, Brazil.
Jazyk:	angličtina
Zdroj:	Intractable & rare diseases research [Intractable Rare Dis Res] 2021 Aug; Vol. 10 (3), pp. 179-189.
DOI:	10.5582/irdr.2021.01012
Abstrakt:	Fibrodysplasia Ossificans Progressiva (FOP) is a rare congenital intractable disease associated with a mutation in ACVR1 gene, characterized by skeleton malformations. Ascorbic acid (AA) and propranolol (PP) in combination is reported to minimize flare-ups in patients. FOP leukocyte phenotype may possibly be modulated by AA and PP treatment. In this study, expression of 22 potential target genes was analyzed by RT-PCR in peripheral blood mononuclear cells culture (PBMC) from FOP patients and controls to determine effectiveness of the combination therapy. PBMC were treated with AA, PP and AA+PP combination. Basal expression of 12 of the 22 genes in FOP PBMC was statistically different from controls. ACVR1 , ADCY2 , ADCY9 and COL3 were downregulated while COL1 was upregulated. ADRB1 , ADRB2 , RUNX2 , TNF-α and ACTB , were all overexpressed in FOP PBMC. In control, AA upregulated COL1, SVCT1, ACTB, AGTR2 and downregulated ADCY2 . In FOP cells, AA upregulated ACVR1, BMP4, COL1, COL3, TNF-α , ADCY2, ADCY9, AGTR2 and MAS , while downregulated ADBR2, RUNX2, ADCY1, SVCT1 and ACTB . PP increased ADBR1 and decreased RUNX2, TNF-α, AGTR1, ACTB and CHRNA7 genes in treated control PBMC compared to untreated. PP upregulated ADBR1, ADBR2 and MAS , and downregulated TNF-α and ACTB in treated FOP PBMC versus untreated. AA+PP augmented ADRB1 and ADRB2 expressions in control PBMC. In FOP PBMC, AA+PP augmented ACVR1, COL1, COL3, ADBR1, AGTR2 and MAS expression and downregulated ADBR2, RUNX2, ACTB and MRGD . These data show distinct gene expression modulation in leukocytes from FOP patients when treated with AA and or PP. Competing Interests: The authors have no conflicts of interest to disclose. (2021, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)
Databáze:	MEDLINE
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