Regenerative Medicine of Nephron Segments

缺血性急性肾功能衰竭（ARF）是成人中最常见的ARF形式。缺血性肾损伤后小管再生的分子机制在很大程度上仍然未知。为了恢复器官或组织功能，再生过程可能概括了发育过程。成体小管上皮细胞在细胞损伤后具有强大的再生能力。我们检测了两个发育基因Wnt-4和Ets-1在ARF肾小管再生中的功能作用。这张幻灯片显示了肾小管再生机制的假说。肾小管损伤后，如缺血，肾小管细胞凋亡或坏死。然后，部分受损肾小管再生。我们假设了三种肾小管再生的可能性。一个是肾小管干细胞的存在。关于干细胞，在这次会议上已经作了许多报告。第二种可能是去分化。我们的假设是肾小管细胞转化为具有胚胎特征的去分化细胞，如表达Wnt-4和Ets-1。另一种可能是与血细胞有关。总之，我们证明了当肾小管细胞受损时，使用多种类型的干细胞会发生几种恢复机制。我们可以通过操纵诸如组织特异性干细胞、去分化干细胞、骨髓干细胞或胚胎干细胞等干细胞来改善肾小管损伤的恢复。对肾脏再生的进一步了解将有助于改进治疗ARF的新策略。

Ischemic acute renal failure (ARF) is the most common form of ARF in the adult population. The molecular mechanisms of tubular regeneration after ischemic renal injury remain largely unknown. It has been suggested that regeneration processes may recapitulate developmental processes in order to restore organ or tissue function. The adult tubular epithelial cells have a potent ability of regenerate after cellular damage. We examined functional role of two developmental genes, Wnt-4 and Ets-1 in renal tubular regeneration in ARF. This slide shows hypothesis of mechanisms of renal tubular regeneration. After renal tubular injury, such as ischemia, renal tubular cells falls into apoptosis or necrosis. Then, some parts of injured renal tubules regenerate. We hypothesized three possibilities of renal tubular regeneration. One is the presence of renal tubular stem cells. Concerning to the stem cells, mamy presentation have already been reported in this meeting. The second possibility is Dedifferentiation. Our hypothesis is that the renal tubular cells transform to dedifferentiated cells, which have embryonic character, such as expression of Wnt-4 and Ets-1. The other possibility is involvement of blood cells.In summary, we demonstrated that when the renal tubular cells are damaged, several recovery mechanisms are occurs using many types of stem cells. We may improve the recovery of renal tubular damage by manipulating stem cells such as tissue specific stem cells, or dedifferentiated stem cells, bone-marrow deribed stein cells, or ES cells. Further understanding of renal regeneration will improve new therapeutic strategy for ARF.