ROCK inhibitor attenuates carbon blacks-induced pulmonary fibrosis in mice via Rho/ROCK/NF-kappa B pathway

Environ Toxicol. 2021 Jul;36(7):1476-1484. doi: 10.1002/tox.23135. Epub 2021 Mar 31.

Abstract

Exposure to carbon blacks (CBs) has been associated with the progression of pulmonary fibrosis, whereas the mechanism is still not clear. We therefore aimed to investigate the effect of RhoA/ROCK pathway on pulmonary fibrosis caused by CBs exposure. Western blot analysis indicated that CBs could promote the activation of RhoA/ROCK pathway and phosphorylation of p65 and IκBα in mice lung. However, ROCK inhibitor Y-27632 could attenuate phosphorylation levels of p65 and IκBα and restore histopathological changes of the lung tissue. Then, we evaluated the effect of RhoA/ROCK pathway on pulmonary fibrosis by detecting the expression levels of α-SMA, vimentin, and Collagen type-I (Col-I), which could be partly inhibited by Y-27632. It was assumed that inhibition of ROCK could be a promising therapeutic candidate for CBs-induced pulmonary fibrosis, which possibly through the blockage of RhoA/ROCK/NF-κB pathway.

Keywords: NF-kappa B; RhoA/rho kinase; Y-27632; carbon black; pulmonary fibrosis.

MeSH terms

  • Animals
  • Carbon
  • Mice
  • NF-kappa B* / metabolism
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Soot
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • NF-kappa B
  • Soot
  • Carbon
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein