Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Protein box nhóm di động cao 1 làm giảm khả năng ức chế miễn dịch và hiệu quả điều trị của tế bào gốc trung mô trong tổn thương thận cấp tính
Tóm tắt
Tổn thương thận do thiếu máu và tái tưới máu (IRI) là một nguyên nhân phổ biến của tổn thương thận cấp tính và là hệ quả không thể tránh khỏi của việc ghép thận, vẫn còn thiếu các liệu pháp điều trị cụ thể. Gần đây, tế bào gốc trung mô (MSC) đã nổi lên như một liệu pháp dựa trên tế bào hứa hẹn cho IRI trong bối cảnh ghép tạng. MSC điều chỉnh âm tính sự tiết cytokine pro-inflammatory cũng như sự kích hoạt của các tế bào miễn dịch trong quá trình IRI thông qua đặc tính ức chế miễn dịch độc đáo của nó. Chúng tôi đã sử dụng mô hình chuột IRI thận và dòng tế bào MSC để theo dõi các điểm kiểm tra liên quan đến IRI. siRNA được sử dụng để làm giảm các yếu tố chính tiềm tàng cho phân tích cơ chế. Phân tích thống kê được thực hiện bằng cách sử dụng ANOVA một chiều với quy trình Tukey’s post hoc bằng SPSS. Sự biểu hiện của protein hộp nhóm di động cao 1 (HMGB1) tăng lên trong giai đoạn cấp tính cũng như giai đoạn phục hồi của IRI. Quan trọng là, sự tăng biểu hiện HMGB1 có liên quan đến mức độ nghiêm trọng của tổn thương. HMGB1 giảm khả năng ức chế miễn dịch do MSC kích thích trong sự hiện diện của cytokine pro-inflammatory in vitro. Ứng tác của thụ thể Toll như 4 (TLR4) - chất ức chế synthase nitric oxide cảm ứng (iNOS) góp phần vào tác động tiêu cực của HMGB1 đối với MSC. Ức chế tín hiệu HMGB1-TLR4 làm tăng hiệu quả điều trị của MSC trong mô hình IRI thận chuột. Những phát hiện này chứng tỏ rằng HMGB1 đóng vai trò quan trọng trong việc định hình các thuộc tính điều hòa miễn dịch của MSC trong các môi trường vi mô, cung cấp cái nhìn mới về sự tương tác giữa MSC và các thành phần môi trường vi mô, cho thấy tín hiệu HMGB1 là một mục tiêu tiềm năng để cải thiện liệu pháp dựa trên MSC.
Từ khóa
#thận #tổn thương do thiếu máu-tái tưới máu #tế bào gốc trung mô #protein hộp nhóm di động cao 1 #ức chế miễn dịchTài liệu tham khảo
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