Indoxyl sulfate impairs in vitro erythropoiesis by triggering apoptosis and senescence
Issued Date
2022-08-01
Resource Type
ISSN
15353702
eISSN
15353699
Scopus ID
2-s2.0-85131058179
Pubmed ID
35611811
Journal Title
Experimental Biology and Medicine
Volume
247
Issue
15
Start Page
1350
End Page
1363
Rights Holder(s)
SCOPUS
Bibliographic Citation
Experimental Biology and Medicine Vol.247 No.15 (2022) , 1350-1363
Suggested Citation
Duangchan T., Rattanasompattikul M., Chitchongyingcharoen N., Mas-Oodi S., Promkan M., Rongkiettechakorn N., Korpraphong S., Supokawej A. Indoxyl sulfate impairs in vitro erythropoiesis by triggering apoptosis and senescence. Experimental Biology and Medicine Vol.247 No.15 (2022) , 1350-1363. 1363. doi:10.1177/15353702221097320 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/87489
Title
Indoxyl sulfate impairs in vitro erythropoiesis by triggering apoptosis and senescence
Author's Affiliation
Other Contributor(s)
Abstract
Anemia is a major complication in over 50% of chronic kidney disease (CKD) patients. One of the main causes of anemia in CKD is the reduction of erythropoietin (EPO) synthesis from renal tubular cells. Therefore, first-line treatment of CKD is EPO administration; however, EPO unresponsiveness in several patients is frequently found. More undefined causes of anemia in CKD are under interest, especially uremic toxins, which are a group of solutes accumulated in CKD patients. The highly detectable protein-bound uremic toxin, indoxyl sulfate (IS) was investigated for its effects on in vitro erythropoiesis in this study. CD34+ hematopoietic stem cells were isolated from human umbilical cord blood and differentiated toward erythrocyte lineage for 14 days in various concentrations of IS (12.5, 25, 50, and 100 µg/mL). The effects of IS on cell proliferation, differentiation, apoptosis, and senescence were determined. Cell proliferation was investigated by manual cell counting. Cell surface marker expression was analyzed by flow cytometry. Wright’s staining was performed to evaluate cell differentiation capacity. Apoptosis and senescence marker expression was measured using reverse transcription polymerase chain reaction (RT-PCR). TUNEL assay was performed to detect apoptotic DNA fragmentation. Our results demonstrated that IS reduced cell proliferation and impaired erythrocyte differentiation capacity. In addition, this study confirmed the effects of IS on cell apoptosis and senescence during erythropoietic differentiation. Therefore, the promotion of apoptosis and senescence might be one of the possible mechanisms caused by uremic toxin accumulation leading to anemia in CKD patients.