Angiotensin II Promotes Progressive Activation of Fibrogenic Periostin-Lineage Cells in Lung and Kidney

Abstract

Angiotensin II (AngII), the primary effector of the renin-angiotensin system, is essential for maintaining blood pressure and fluid-electrolyte homeostasis. However, elevated AngII levels are a feature of disease conditions such as heart failure and chronic kidney disease, where it is associated with pathological tissue remodeling and fibrosis. AngII-mediated fibrosis has been documented in multiple organs and is characterized by fibroblast expansion, myofibroblast differentiation, and excessive extracellular matrix deposition. Periostin has recently emerged as a marker of fibroblast activation. Notably, periostin expression is highly upregulated during fibrotic remodeling in the kidney and lung, which is strongly linked with impaired organ function. While AngII-induced activation of periostin-lineage (PostnLin) cells is well established in the heart, the temporal dynamics of PostnLin activation in response to AngII infusion in the lung and kidney remain unexplored. Here, we used a Postn-MerCreMer lineage-tracing approach, combined with continuous AngII infusion over an experimental period of one week and two weeks to assess PostnLin responses in lung and kidney. Our findings reveal a progressive activation of PostnLin cells in both organs, characterized by myofibroblast phenotype, together with increased collagen deposition and macrophage infiltration. These results highlight the potential of PostnLin fibroblasts as a key effector of AngII-mediated tissue remodeling and fibrosis in the lung and kidney.