Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway

Cell Adh Migr. 2020 Dec;14(1):42-56. doi: 10.1080/19336918.2020.1721172.

Abstract

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-κB 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 IκBα phosphorylation. Moreover, si-RhoA also suppressed the expression of pro-inflammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IκBα. In conclusion, thymol inhibits AGE-induced cell injury in HPCs by suppressing the RhoA-NF-κB pathway and may be apromising therapeutic agent.

Keywords: RhoA/ROCK pathway; Thymol; advanced glycation end products (AGE); human podocytes; nuclear factor-kappa B (NF-κB).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Cytoskeleton / metabolism
  • Glycation End Products, Advanced / toxicity*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • NF-kappa B / metabolism*
  • Podocytes / pathology*
  • Protective Agents / pharmacology
  • RNA, Small Interfering / metabolism
  • Signal Transduction* / drug effects
  • Thymol / chemistry
  • Thymol / pharmacology*
  • Vimentin / metabolism
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Cytokines
  • Glycation End Products, Advanced
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NF-kappa B
  • NPHS2 protein
  • Protective Agents
  • RNA, Small Interfering
  • Vimentin
  • nephrin
  • Thymol
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein

Grants and funding

This work was supported by the grant to Bing Chen from the Primary Research & Development Plan of Shandong Province (2018GSF118227) and by a grant to Rong Wang from the National Natural Science Foundation (Grant No. 81770723)