Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells.
Human amniotic fluid stem cells (AFSC) are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS) and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(P)H oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4) depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage.
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
Tullia
T
Maraldi
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy ; EURAC Research, Center for Biomedicine, Via Galvani 31, 39100 Bolzano, Italy.
Marianna
M
Guida
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
Manuela
M
Zavatti
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
Elisa
E
Resca
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
Laura
L
Bertoni
Unit of Obstetrics & Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Viale Umberto I 50, 42123 Reggio Emilia, Italy ; University of Modena e Reggio Emilia, Viale A. Allegri 9, 42121 Reggio Emilia, Italy.
Giovanni B
GB
La Sala
Department of Surgical, Medical, Dental and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via Del Pozzo 71, 41100 Modena, Italy.
Anto
A
De Pol
D000653:Amniotic Fluid / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human