海洋深層水通過IGF1R的表現強化間葉幹細胞的能力以調節microRNA-880-3p治療老化所造成的心臟疾病

Abstract

衰老是降低心臟功能的原因之一，幹細胞療法可能為治療由衰老引起的心臟功能障礙提供更光明的未來。海洋深層水（DSW）顯示出對細胞保護的有益作用，但細胞機制仍不清楚。這項研究旨在研究用海洋深層水（DSW）預處理的間葉幹細胞是否比未經海洋深層水（DSW）預處理的間葉幹細胞具有更好的心臟保護作用。在細胞研究中，我們發現深海水通過膜蛋白胰島素樣生長因子1受體（IGF1R）的表達提高幹細胞活力。此外，我們證實miR-880-3p在老年心肌細胞中表現量增加。在與幹細胞共培養的老年心肌細胞中，我們發現海洋深層水（DSW）預處理的幹細胞顯著降低了老年心肌細胞中衰老的miR-880-3p的表現，從而導致了心肌細胞功能的恢復。在動物研究中，在治療老年的大鼠心臟中，我們發現海洋深層水（DSW）預處理的幹細胞顯著降低了老年心臟中老化的蛋白表現與纖維化表現，從而導致了心臟功能的恢復。此外，我們也證實海洋深層水（DSW）預處理的幹細胞能夠修復心臟中細胞雜亂的排列與細胞數量。Aging is one of causative agents in reducing heart functions and stem cell therapy may provide a brighter future in the treatment of heart dysfunction induced by aging. Deep sea water shows beneficial effect on cell protection but the cellular mechanism remains unclear. This study aims to investigate if mesenchymal stem cells pre-treated with deep sea water show better cardio-protective effect than stem cells without deep sea water pre-treatment. In cell studies, we found that deep sea water increases stem cell viability through expression of membrane protein insulin-like growth factor 1 receptor (IGF1R). In addition, we confirmed that miR-880-3p is upregulated in aged cardiomyocytes. In aged cardiomyocytes co-culture with stem cells, we found that stem cells with deep sea water pre-treatment significantly reduce expression of senescent miR-880-3p in aged cardiomyocytes, leading to recovery of cardiomyocyte ability. In animal studies, In the treatment of aged rat hearts, we found that stem cells pretreated with deep sea water (DSW) significantly reduced the expression of aging protein and fibrosis in the aged heart, which led to the recovery of cardiac function. In addition, we also confirmed that stem cells pre-treated with deep sea water (DSW) can repair the disordered arrangement and number of cells in the heart.