Open AccessTransplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF ‐κB pathway
Author(s) -
Wang Lei,
Yang Mengnan,
Jin Minfei,
Wu Yuelin,
Zheng Tao,
Gu Shengyi,
Hua Xiaolin
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13574
Subject(s) - gene knockdown , transplantation , biology , regeneration (biology) , chromatin immunoprecipitation , growth factor , microbiology and biotechnology , cancer research , andrology , gene expression , medicine , receptor , cell culture , promoter , gene , biochemistry , genetics
To investigate the potential beneficial effect of insulin‐like growth factor‐1 ( IGF ‐1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSC s were isolated and cultured. The relative expressions of IGF ‐1 and IL ‐10 were determined by RT ‐ PCR and immunoblotting. The secretory IL ‐10 and released E2 were measured using ELISA kits. The relative vWF and α‐ SMA expressions were determined by immunohistochemistry. The direct binding of NF ‐κB subunit p50 with IL ‐10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL ‐10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF ‐1 expression in BMSC s induced IL ‐10 expression and secretion, which was further enhanced by E2‐ PLGA . IGF ‐1 overexpression improved BMSC s transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF ‐1‐induced expression and secretion of IL ‐10 in BMSC s, which consequently compromised the IGF ‐1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL ‐10 expression via direct association with its promoter. Our data suggested that transplantation of IGF ‐1 overexpressing BMSC s improved functional regeneration of injured uterus by inducing IL ‐10 expression and secretion via activation of NF ‐κB signalling.