How tubular epithelial cells dictate the rate of renal fibrogenesis?

The main threat to a kidney injury, whatever its cause and regardless of whether it is acute or chronic, is the initiation of a process of renal fibrogenesis, since fibrosis can auto-perpetuate and is of high prognostic significance in individual patients. In the clinic, a decrease in glomerular filtration rate correlates better with tubulointerstitial damage than with glomerular injury. Accumulation of the extracellular matrix should not be isolated from other significant cellular changes occurring in the kidney, such as infiltration by inflammatory cells, proliferation of myofibroblasts, obliteration of peritubular capillaries and atrophy of tubules. The aim of this review is to focus on tubular epithelial cells (TEC), which, necessarily involved in the repair process, eventually contribute to accelerating fibrogenesis. In the context of injury, TEC rapidly exhibit phenotypic and functional changes that recall their mesenchymal origin, and produce several growth factors known to activate myofibroblasts. Because they are high-demanding energy cells, TEC will subsequently suffer from the local hypoxia that progressively arises in a microenvironment where the matrix increases and capillaries become rarified. The combination of hypoxia and metabolic acidosis may induce a vicious cycle of sustained inflammation, at the center of which TEC dictate the rate of renal fibrogenesis.