PMID- 33609619 OWN - NLM STAT- MEDLINE DCOM- 20210423 LR - 20210423 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 173 DP - 2021 Mar TI - Human umbilical cord mesenchymal stem cells attenuate podocyte injury under high glucose via TLR2 and TLR4 signaling. PG - 108702 LID - S0168-8227(21)00055-3 [pii] LID - 10.1016/j.diabres.2021.108702 [doi] AB - 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-1beta, TNF-alpha, 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. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Wang, Yinghui AU - Wang Y AD - 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. FAU - Liu, Jiaxi AU - Liu J AD - Graduate School of Arts and Sciences, Columbia University, USA. FAU - Zhang, Qingqing AU - Zhang Q AD - 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. FAU - Wang, Weiwei AU - Wang W AD - Zibo Central Hospital, Shandong, China. FAU - Liu, Qingzhen AU - Liu Q AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. FAU - Liu, Shanshan AU - Liu S AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. FAU - Song, Yan AU - Song Y AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. FAU - Wang, Xueling AU - Wang X AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. FAU - Zhang, Yaping AU - Zhang Y AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. FAU - Li, Shan AU - Li S AD - 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. FAU - Yang, Xue AU - Yang X AD - 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. FAU - Lv, Shasha AU - Lv S AD - Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. Electronic address: shasha0369@163.com. FAU - Liu, Gang AU - Liu G AD - 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. LA - eng PT - Journal Article DEP - 20210218 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Disease Models, Animal MH - Fetal Blood/*metabolism MH - Glucose/*metabolism MH - Humans MH - Inflammation/metabolism MH - Male MH - Mesenchymal Stem Cells/*metabolism MH - Mice MH - Podocytes/*metabolism MH - Signal Transduction MH - Toll-Like Receptor 2/*metabolism MH - Toll-Like Receptor 4/*metabolism OTO - NOTNLM OT - Diabetic nephropathy OT - Hepatocyte growth factor OT - Inflammation OT - Mesenchymal stem cells OT - Podocytes OT - Toll-like receptors EDAT- 2021/02/21 06:00 MHDA- 2021/04/24 06:00 CRDT- 2021/02/20 20:09 PHST- 2020/08/07 00:00 [received] PHST- 2021/01/07 00:00 [revised] PHST- 2021/02/04 00:00 [accepted] PHST- 2021/02/21 06:00 [pubmed] PHST- 2021/04/24 06:00 [medline] PHST- 2021/02/20 20:09 [entrez] AID - S0168-8227(21)00055-3 [pii] AID - 10.1016/j.diabres.2021.108702 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2021 Mar;173:108702. doi: 10.1016/j.diabres.2021.108702. Epub 2021 Feb 18.