TY - JOUR
T1 - Novel regulations of MEF2-A, MEF2-D, and CACNA1S in the functional incompetence of adipose-derived mesenchymal stem cells by induced indoxyl sulfate in chronic kidney disease
AU - Thi Do, Duyen
AU - Phan, Nam Nhut
AU - Wang, Chih Yang
AU - Sun, Zhengda
AU - Lin, Yen Chang
N1 - Publisher Copyright:
© 2016, Springer Science+Business Media Dordrecht.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Indoxyl sulfate (IS) is a digestive intermediate product that is a known indicator of chronic kidney disease. Its toxicity has also been suggested to accelerate chronic kidney disease. Recently, mesenchymal stem cells (MSCs) have been confirmed as a potential treatment in kidney regeneration. To determine the universal alteration in gene expression, we combined high-throughput microarray technology and in vitro culture of adipose-derived mesenchymal stem cells at different doses of IS (20, 40, 60 mg/l). We found that indoxyl sulfate has a remarkable interconnection with stem cell and calcium/calmodulin-dependent kinase pathways. In vitro results showed that indoxyl sulfate exerts anti-proliferation and anti-migration effects on ADMSCs. In addition, IS effects lead to increase in apoptotic cells and cells arrested at the G1 phase. Moreover, MEF2-A, MEF2-D and CACNA1S expression significantly decreased after indoxyl sulfate treatment. It can be speculated that following treatment with indoxyl sulfate, the function of ADMSCs is decreased and ADMSCs’ ability to support renal tubule regeneration in chronic kidney disease patients may be lower.
AB - Indoxyl sulfate (IS) is a digestive intermediate product that is a known indicator of chronic kidney disease. Its toxicity has also been suggested to accelerate chronic kidney disease. Recently, mesenchymal stem cells (MSCs) have been confirmed as a potential treatment in kidney regeneration. To determine the universal alteration in gene expression, we combined high-throughput microarray technology and in vitro culture of adipose-derived mesenchymal stem cells at different doses of IS (20, 40, 60 mg/l). We found that indoxyl sulfate has a remarkable interconnection with stem cell and calcium/calmodulin-dependent kinase pathways. In vitro results showed that indoxyl sulfate exerts anti-proliferation and anti-migration effects on ADMSCs. In addition, IS effects lead to increase in apoptotic cells and cells arrested at the G1 phase. Moreover, MEF2-A, MEF2-D and CACNA1S expression significantly decreased after indoxyl sulfate treatment. It can be speculated that following treatment with indoxyl sulfate, the function of ADMSCs is decreased and ADMSCs’ ability to support renal tubule regeneration in chronic kidney disease patients may be lower.
KW - Chronic kidney disease
KW - Indoxyl sulfate
KW - Kidney regeneration
KW - L-type calcium channel
KW - Mesenchymal stem cell
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U2 - 10.1007/s10616-016-9983-0
DO - 10.1007/s10616-016-9983-0
M3 - Article
AN - SCOPUS:84983507737
SN - 0920-9069
VL - 68
SP - 2589
EP - 2604
JO - Cytotechnology
JF - Cytotechnology
IS - 6
ER -