PMID- 32028827 OWN - NLM STAT- MEDLINE DCOM- 20210601 LR - 20210601 IS - 1933-6926 (Electronic) IS - 1933-6918 (Print) IS - 1933-6918 (Linking) VI - 14 IP - 1 DP - 2020 Dec TI - Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-kappaB-mediated by RhoA/ROCK signalling pathway. PG - 42-56 LID - 10.1080/19336918.2020.1721172 [doi] AB - Advanced glycation end products (AGE) are those of the most powerful pathogenic factors that related to diabetic complications. In our study, we investigated the beneficial effects of thymol on AGE induced cell injury and apoptosis in human podocytes (HPCs) and attempted to clarify its mechanisms. Our results revealed that stimulation with AGE could significantly activate RhoA/NF-kappaB pathway. Results showed thymol could markedly suppress inflammatory responses, cell apoptosis and disordered cytoskeleton. Also thymol restored the expression of podocin, restrained migration capacity. Western blot analysis indicated that it could restore the expression of RhoA, ROCK and vimentin, nephrin, podocin and p65 and IkappaBalpha phosphorylation. Moreover, si-RhoA also suppressed the expression of pro-inflammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IkappaBalpha. In conclusion, thymol inhibits AGE-induced cell injury in HPCs by suppressing the RhoA-NF-kappaB pathway and may be apromising therapeutic agent. FAU - Wang, Qinglian AU - Wang Q AD - Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. FAU - Shen, Zhenwei AU - Shen Z AD - Department of Biostatistics, WuXi Clinical Development Service (Shanghai) Co., Ltd, Shanghai, China. FAU - Qi, Guanghui AU - Qi G AD - Department of Urological Surgery, The First Hospital of Zibo, Shandong, China. FAU - Zhao, Yanfang AU - Zhao Y AD - Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. FAU - Zhang, Hongge AU - Zhang H AD - Department of Urological Surgery, Tengzhou Hospital of Traditional Chinese Medicine, Zaozhuang, China. FAU - Wang, Rong AU - Wang R AD - Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Adh Migr JT - Cell adhesion & migration JID - 101469464 RN - 0 (Cytokines) RN - 0 (Glycation End Products, Advanced) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (NF-kappa B) RN - 0 (NPHS2 protein) RN - 0 (Protective Agents) RN - 0 (RNA, Small Interfering) RN - 0 (Vimentin) RN - 0 (nephrin) RN - 3J50XA376E (Thymol) RN - EC 2.7.11.1 (rho-Associated Kinases) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Cell Line MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Cytokines/metabolism MH - Cytoskeleton/metabolism MH - Glycation End Products, Advanced/*toxicity MH - Humans MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Membrane Proteins/metabolism MH - NF-kappa B/*metabolism MH - Podocytes/*pathology MH - Protective Agents/pharmacology MH - RNA, Small Interfering/metabolism MH - *Signal Transduction/drug effects MH - Thymol/chemistry/*pharmacology MH - Vimentin/metabolism MH - rho-Associated Kinases/*metabolism MH - rhoA GTP-Binding Protein/*metabolism PMC - PMC7757830 OTO - NOTNLM OT - RhoA/ROCK pathway OT - Thymol OT - advanced glycation end products (AGE) OT - human podocytes OT - nuclear factor-kappa B (NF-kappaB) EDAT- 2020/02/08 06:00 MHDA- 2021/06/02 06:00 PMCR- 2020/02/07 CRDT- 2020/02/08 06:00 PHST- 2020/02/08 06:00 [entrez] PHST- 2020/02/08 06:00 [pubmed] PHST- 2021/06/02 06:00 [medline] PHST- 2020/02/07 00:00 [pmc-release] AID - 1721172 [pii] AID - 10.1080/19336918.2020.1721172 [doi] PST - ppublish SO - Cell Adh Migr. 2020 Dec;14(1):42-56. doi: 10.1080/19336918.2020.1721172.