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.

A novel role of vitronectin in promoting survival of mesenchymal stem cells under serum deprivation stress

“…In contrast, Oskowitz et al reported a unique phenomenon by which human bone marrow MSCs not only survived for prolonged periods but also secreted pro-survival and angiogenic factors under serum-deprived conditions [26]. Later, another study proposed that ulinastatin was able to promote survival of MSCs under serum deprivation state [27], and similarly, BMP signaling pathway was indicated to be involved in survival of human MSCs in serum-free medium [28]. We also recently showed that WJ-MSCs retained a significant level of viable cells under the harsh ischemia-like conditions in vitro, with a strong upregulation of VTN [7].…”

Study on the inhibitory effect of ulinastatin on caspase-1-dependent pyroptosis in acinar cells of acute pancreatitis

“…Previous studies have shown that ulinastatin can reduce apoptosis by inhibiting caspase-3 activation. 23 Recent studies have also shown that ulinastatin can inhibit the inflammatory activation induced by lipopolysaccharide. 24 These results also suggest the possible intervention pathway of ulinastatin on pyroptosis.…”

Ulinastatin protects against myocardial ischemia/reperfusion injury in rats via Rho/ROCK signaling pathway

“…Ulinastatin reduces the release and represses the activity of elastase in leukocytes, especially polymorphonuclear neutrophils. Moreover, it is able to stabilize the lysosomal membrane and restrain the release of lysosomal enzymes (4,5). Although previous studies have manifested that ulinastatin exerts beneficial effects on IRI of the lung (6), liver (7) and kidney (8), the impact mechanism of ulinastatin on myocardial IRI still remains unclear.…”