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World J Nephrol. Jul 6, 2015; 4(3): 367-373
Published online Jul 6, 2015. doi: 10.5527/wjn.v4.i3.367
How tubular epithelial cells dictate the rate of renal fibrogenesis?
Kevin Louis, Alexandre Hertig
Kevin Louis, Alexandre Hertig, AP-HP, Hôpital Tenon, Urgences Néphrologiques et Transplantation Rénale, F-75020 Paris, France
Alexandre Hertig, UPMC Sorbonne Université Paris 06, UMR S 1155, F-75020 Paris, France
Author contributions: Both authors contributed to this manuscript.
Conflict-of-interest statement: I declare, as the corresponding author, that neither I nor Kevin Louis have any conflict of interest with regard to the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alexandre Hertig, Professor, UPMC Sorbonne Université Paris 06, UMR S 1155, 4 rue de la Chine, F-75020 Paris, France. alexandre.hertig@upmc.fr
Telephone: +33-15-6016695 Fax: +33-15-6017968
Received: February 10, 2015
Peer-review started: February 11, 2015
First decision: March 20, 2015
Revised: May 6, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: July 6, 2015
Processing time: 145 Days and 23.6 Hours
Abstract

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.

Keywords: Epithelium; Fibroblasts; Acute kidney injury; Chronic kidney diseases; Fibrosis

Core tip: In this review, we explain why and how tubular epithelial cells should be regarded not only as victims in the context of chronic kidney disease, but also as actors playing an ambiguous role. In particular, we report on studies which demonstrated that they can actively contribute to fibrogenesis itself, either directly, because their function has been reprogrammed in a way reminiscent of their mesenchymal origin, or from a distance, by influencing endothelial and myofibroblast functions. Last, they are seen as potential targets for new drugs aiming at controlling fibrosis.