| Summary: | 碩士 === 中國文化大學 === 生物科技研究所 === 102 === Backgrounds: Indoxyl Sulfate (IS) is a protein metabolite in patients with chronic renal insufficiency. It also is a uremic toxin that has been suggested to promote the progression of chronic kidney disease (CKD). Accumulation of IS in CKD patients negatively affects various organ systems, including the cardiovascular system. It has become a worldwide public health problem, causing considerable morbidity and mortality. Renal transplantation is the treatment of choice for end-stage renal disease, but is limited by a small number of organ donors and the immune barrier. Recently however, Mesenchymal Stem Cells (MSCs) have been confirmed to aid in kidney regeneration. This study aims to investigate the effects of IS in adipose-derived mesenchymal stem cells (ADMSCs), whether ADMSCs will remain functionally competent when exposed to the same conditions as patients with differing stages of CKD in vitro. Materials and Methods: ADMSCs were cultured in the presence of IS of differing concentrations. Cell proliferation, apoptosis, cell cycle, and regenerative qualities were measured. Results: We found that IS exerts anti-proliferation, anti-migration effects on ADMSCs. In addition, uremic ADMSCs have an increase in apoptotic cells and were arrested to G1 phase. Moreover, the protein expression of myocyte enhancer factor-2 (MEF2-A, MEF2-D) proteins and CACNA1S subunit of L-type calcium channel were significantly decreased after IS treatment. The results from our present study may be of some relevance in understanding the molecular mechanisms leading to the changes in ADMSCs induced by IS. Conclusion: Taken together, the results clearly demonstrate that following treatment with IS, the functional incompetence of ADMSCs is increased and the ability of ADMSCs to support renal tubule regeneration in CKD patients may decrease.
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