UUO induces lung fibrosis with macrophage-myofibroblast transition in rats

Int Immunopharmacol. 2021 Apr:93:107396. doi: 10.1016/j.intimp.2021.107396. Epub 2021 Feb 1.

Abstract

Progression of chronic kidney disease (CKD) to uremia is often accompanied by varying degrees of lung damage and this is also an important cause of death. Although there are many studies on the mechanism of lung injury, it is not clearly understood. Inflammatory macrophages may associated with fibrosis in the lungs. Here, we investigated the role of macrophage-myofibroblast transition (MMT) in lung fibrosis with unilateral ureteral obstruction (UUO) rats. We found that cells undergoing MMT accounted for an important part of the myofibroblast population, and correlated with lung fibrosis, MMT cells in lungs have a predominant M2 phenotype, and this process was attenuated after treatment with eplerenone. In conclusion, our studies provide a possible mechanism for UUO-induced kidney damage and lung injury, indicating the possibility of using eplerenone, a mineralocorticoid receptor blocker, to treat UUO to reduce kidney damage and protect lung function.

Keywords: Eplerenone; Macrophage-myofibroblast transition; Mineralocorticoid receptor; Pulmonary fibrosis; Unilateral ureteral obstruction.

MeSH terms

  • Animals
  • Cell Differentiation
  • Disease Models, Animal
  • Eplerenone / therapeutic use*
  • Humans
  • Macrophages / immunology*
  • Male
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Myofibroblasts / immunology*
  • Protective Agents / therapeutic use
  • Pulmonary Fibrosis / drug therapy
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / immunology*
  • Rats
  • Rats, Wistar
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / immunology*
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / drug therapy
  • Ureteral Obstruction / immunology*

Substances

  • Mineralocorticoid Receptor Antagonists
  • Protective Agents
  • Eplerenone