Signaling Crosstalk between Tubular Epithelial Cells and Interstitial Fibroblasts after Kidney Injury

A wide variety of kidney diseases ultimately lead to tubulointerstitial damage. The initial site of injury is usually the renal tubules, with activation of fibroblasts occurring later. Self-limited disease is characterized by transient cellular activation with timed deactivation and ultimately a return to normal functioning, whereas sustained responses characterize chronic disease and the development of irreversible fibrosis. The underlying molecular and cellular mechanisms of this cascade of events remain an area of active research. Current data overwhelmingly support a role for crosstalk between the tubular epithelium and the interstitial fibroblast that mediates both repair/regeneration and progressive disease. This epithelial-mesenchymal communication (EMC) is regulated by a variety of soluble ligands binding to cell surface receptors to induce intracellular signaling events.