Hewitson Tim D
Department of Nephrology, Royal Melbourne Hospital & Department of Medicine, University of Melbourne, Melbourne, Australia.
Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S14. doi: 10.1186/1755-1536-5-S1-S14. eCollection 2012.
Fibrotic disorders are commonplace, take many forms and can be life-threatening. No better example of this exists than the progressive fibrosis that accompanies all chronic renal disease. Renal fibrosis is a direct consequence of the kidney's limited capacity to regenerate after injury. Renal scarring results in a progressive loss of renal function, ultimately leading to end-stage renal failure and a requirement for dialysis or kidney transplantation. Although it manifests itself histologically as an increase in extracellular matrix, we know that the histological appearance can be caused by a de novo synthesis of matrix (primarily collagen), or a disproportionate loss of renal parenchyma. In both cases the process depends on a resident mesenchymal cell, the so-called myofibroblast, and is independent of disease etiology. Potentially we can ameliorate fibrosis, either indirectly by modifying the environment the kidney functions in, or more directly by interfering with activation and function of myofibroblasts. However, while renal fibrosis shares many features in common with the wound healing response in other organs, we also recognise that the consequences can be highly kidney specific. This review highlights the similarities and differences between this process in the kidney and other organs, and considers the therapeutic implications.
纤维化疾病很常见，形式多样，且可能危及生命。伴随所有慢性肾病的进行性纤维化就是最好的例证。肾纤维化是肾脏损伤后再生能力有限的直接后果。肾瘢痕形成导致肾功能逐渐丧失，最终导致终末期肾衰竭，并需要进行透析或肾脏移植。尽管从组织学上看，它表现为细胞外基质增加，但我们知道这种组织学表现可能是由基质（主要是胶原蛋白）的重新合成引起的，也可能是肾实质不成比例地丢失所致。在这两种情况下，该过程都依赖于一种驻留间充质细胞，即所谓的肌成纤维细胞，且与疾病病因无关。我们有可能通过间接改变肾脏功能所处的环境，或者更直接地通过干扰肌成纤维细胞的激活和功能来改善纤维化。然而，虽然肾纤维化与其他器官的伤口愈合反应有许多共同特征，但我们也认识到其后果可能具有高度的肾脏特异性。本综述强调了肾脏与其他器官这一过程的异同，并探讨了其治疗意义。
