Fibrosis, regeneration and cancer: what is the link?
Open Access
- 18 November 2011
- journal article
- review article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 27 (1), 21-27
- https://doi.org/10.1093/ndt/gfr567
Abstract
Tubulo-interstitial fibrosis constitutes the final common pathway for all pathological conditions that evolve towards chronic kidney disease, and transforming growth factor-β1 plays a key role in this process. Furthermore, neutrophil gelatinase-associated lipocalin appears not only to be a simple marker of renal injury but also an active player in disease progression. We are not yet able to control and modulate this phenomenon. Therefore, a better understanding of fibrogenic molecular mechanisms is necessary to detect possible therapeutic strategies that interfere with fibrosis and then stop the progression of renal disease. The line of research called ‘regenerative medicine’ works toward this. According to many authors, the formation of a fibrotic extracellular matrix disrupts the cells’ polarity and stimulates their proliferation, creating conditions for cancer development. However, there is another plausible hypothesis: is it possible that fibrosis provides a sort of ‘protection’ from the development of a cancer as a consequence of the intense proliferation that characterizes any inflammatory process? In superior organisms, and also in humans, regeneration may have been selected negatively and replaced by fibrosis in the course of evolution, to warrant species survival: in fact, unchecked pluripotent cell production and proliferation can lead to tumour development and the potential death of a single individual. Hence, tumours might be the outcome of the failure of fibrotic processes, most likely due to some mediators predominating over others. So, valid experimental models are necessary to understand the interactions that exist between fibrosis and tumours and to evaluate the real advantage of therapies that aim to inhibit the fibrotic process at the renal level or that of other organs. The ideal approach would be to limit fibrosis and then organ function loss but without exposing the patient to risks of developing a tumour, starting from as early as the drugs prescribed.This publication has 61 references indexed in Scilit:
- Cooperative interaction of CTGF and TGF-β in animal models of fibrotic diseaseFibrogenesis & Tissue Repair, 2011
- Pathological Significance of a Panel of Urinary Biomarkers in Patients with Drug-Induced Tubulointerstitial NephritisClinical Journal of the American Society of Nephrology, 2010
- Lipocalin 2 is essential for chronic kidney disease progression in mice and humansJCI Insight, 2010
- Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasisMolecular Cancer, 2010
- Evidence for the Local Evolution of Mechanisms Underlying Limb Regeneration in SalamandersIntegrative and Comparative Biology, 2010
- Regeneration: The origin of cancer or a possible cure?Seminars in Cell & Developmental Biology, 2009
- Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Progression of Chronic Kidney DiseaseClinical Journal of the American Society of Nephrology, 2009
- Regeneration in axolotls: a model to aim for!Experimental Gerontology, 2008
- Snail activation disrupts tissue homeostasis and induces fibrosis in the adult kidneyThe EMBO Journal, 2006
- Chemokines and chemokine receptors are involved in the resolution or progression of renal diseaseKidney International, 2003