Yinghui Wang1, Jiaxi Liu2, Qingqing Zhang1, Weiwei Wang3, Qingzhen Liu4, Shanshan Liu4, Yan Song4, Xueling Wang4, Yaping Zhang4, Shan Li1, Xue Yang1, Shasha Lv5, Gang Liu6. 1. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China. 2. Graduate School of Arts and Sciences, Columbia University, USA. 3. Zibo Central Hospital, Shandong, China. 4. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. 5. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. Electronic address: shasha0369@163.com. 6. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China. Electronic address: lg69007@163.com.
Abstract
AIMS: This research aimed to investigate the effects of high glucose (HG) on the innate immunity of podocytes and diabetic nephropathy (DN) mice via Toll like receptor (TLR) signaling, and explore the protective effectsof human umbilical cord mesenchymal stem cells (HUC-MSCs) on this process. METHODS: HUC-MSCs obtained from human umbilical cord were cocultured with podocytes and transplanted into DN mice. Flow cytometry, CCK-8assay, ELISA, western blot analysis, periodicacid-schiff, masson, immunohistochemistry and immunofluorescence staining was used to detect the inflammation, TLR signaling, physical, biochemical and morphological parameters in podocytes and DN mice. RESULTS: HG reduced the viability of podocytes, activated TLR2 and TLR4 signaling pathway and increased the expression of inflammatory cytokines such as IL-6, IL-1β, TNF-α, and MCP-1 in podocytes and DN mice. However, HUC-MSCs decreased the inflammation and restrained the TLR signaling pathway caused by HG in vitro and in vivo. Furthermore the rhHGF decreased the expression of TLR2 and TLR4 while the blockade of HGF increased the expression of TLR2 and TLR4 in podocytes. CONCLUSIONS: HUC-MSCs have benefits to the podocytes under HG and the progression of DN by inhibiting TLR signaling pathway and depressing the inflammation. HUC-MSCs may be a therapeutic strategy for treating patients with DN.
AIMS: This research aimed to investigate the effects of high glucose (HG) on the innate immunity of podocytes and diabetic nephropathy (DN) mice via Toll like receptor (TLR) signaling, and explore the protective effectsof human umbilical cord mesenchymal stem cells (HUC-MSCs) on this process. METHODS: HUC-MSCs obtained from human umbilical cord were cocultured with podocytes and transplanted into DN mice. Flow cytometry, CCK-8assay, ELISA, western blot analysis, periodicacid-schiff, masson, immunohistochemistry and immunofluorescence staining was used to detect the inflammation, TLR signaling, physical, biochemical and morphological parameters in podocytes and DN mice. RESULTS: HG reduced the viability of podocytes, activated TLR2 and TLR4 signaling pathway and increased the expression of inflammatory cytokines such as IL-6, IL-1β, TNF-α, and MCP-1 in podocytes and DN mice. However, HUC-MSCs decreased the inflammation and restrained the TLR signaling pathway caused by HG in vitro and in vivo. Furthermore the rhHGF decreased the expression of TLR2 and TLR4 while the blockade of HGF increased the expression of TLR2 and TLR4 in podocytes. CONCLUSIONS: HUC-MSCs have benefits to the podocytes under HG and the progression of DN by inhibiting TLR signaling pathway and depressing the inflammation. HUC-MSCs may be a therapeutic strategy for treating patients with DN.