Ulinastatin inhibits apoptosis induced by serum deprivation in mesenchymal stem cells.

Abstract

Mesenchymal stem cells (MSCs) have exhibited great potential in the therapy of cardiovascular disease. However, the application of MSCs is hampered by apoptosis, which reduces the number of cells in the host cardiac microenvironment. Ulinastatin (UTI), a broad‑spectrum protease inhibitor that can be purified from human urine, has attracted attention for its protective effects through its immunomodulatory and anti‑inflammatory properties. The present study aimed to evaluate the effects of UTI on serum deprivation‑induced apoptosis of MSCs and investigate its molecular mechanisms. Cell viability was determined by the MTT assay. Apoptosis was assessed by flow cytometric analysis with Annexin V/propidium iodide staining. The protein levels of cleaved caspase‑3, B‑cell lymphoma‑2 (Bcl‑2) family proteins, total‑Akt and phospho‑Akt were evaluated by western blot. The results of the present study demonstrated that UTI exhibited a protective effect in serum deprived MSCs, as indicated by increased cell viability, and a reduction in the rate of apoptosis and caspase‑3 activation. In addition, treatment with UTI significantly decreased the expression levels of Bcl‑2, Bcl‑extra large and Bcl‑associated X protein. Furthermore, activation of the Akt signaling pathway was involved in the UTI‑induced anti‑apoptotic effects. The present findings indicated that UTI is able to promote the survival of MSCs under serum deprivation conditions. The present study may be helpful in improving the therapeutic efficacy of MSC transplantation used to cure chronic ischemic heart disease.