Drug Design, Development and Therapy (Jan 2020)
KGF Is Delivered to Inflammatory and Induces the Epithelial Hyperplasia in Trinitrobenzene Sulfonic Acid-Induced Ulcerative Colitis Rats
Abstract
Kai Jia,* Yan Wang,* Xin Tong, Rong Wang Department of Nutrition, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai JiaDepartment of Nutrition, Beijing Chao-Yang Hospital, No. 8 Gongti South Road, Chaoyang District, Beijing 100020, People’s Republic of ChinaTel +86-85231275Fax +86-10-83911276Email [email protected]: KGF-modified MSCs can promote the repair of spinal cord injury and pulmonary fibrosis injury in rats. However, the effect of KGF-modified MSCs on UC rats is unclear. We aimed to explore the therapeutic effect and possible mechanism of KGF gene-modified MSCs on trinitrobenzene sulfonic acid (TNBS)-induced UC rats.Methods: The lentivirus-mediated KGF gene was introduced into bone marrow MSCs of male rats. Female SD rats were induced to establish a UC model by TNBS. Untreated MSCs, MSCs carrying empty vectors (MSCs-vec) or MSCs carrying KGF gene (MSCs-KGF) were transplanted into UC rats by tail vein injection.Results: Significantly high expression of KGF was observed in the intestinal tissues of the MSCs-KGF group. Compared with the challenged control group, the DAI score, CMDI score and TDI score of the MSCs group, MSCs-vec group and MSCs-KGF group were markedly lower. Treatment with MSCs obviously promoted the expression of claudin-1 and PCNA in intestinal tissues of UC rats. Simultaneously, compared with the challenged control group, the levels of TNF-α, IL-6 and IL-8 in the intestinal tissues of the MSCs groups were significantly decreased, while the levels of IL-10 were significantly increased. Most importantly, we found that MSCs-KGF significantly improved colonic morphology and tissue damage and inflammation in UC rats compared with MSCs and MSCs-vec. Further analysis showed that MSCs-KGF clearly promoted phosphorylation of PI3K and Akt and inhibited nuclear translocation of NF-κB in intestinal tissues of UC rats.Discussion: MSCs, especially KGF-modified MSCs, can improve colonic tissue damage in UC rats by promoting intestinal epithelial cell proliferation and reducing colonic inflammatory response, which may be related to activation of PI3K/Akt pathway and inhibition of NF-κB activation.Keywords: ulcerative colitis, bone marrow mesenchymal stem cells, keratinocyte growth factor, gene modification, PI3K/Akt pathway, NF-κB
