Johansson Martin E
Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.
Nephron Exp Nephrol. 2014;126(2):76. doi: 10.1159/000360671. Epub 2014 May 19.
The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of the skin and intestine, where stem cells maintain a continuous flow of new cells from designated niches.
This review discusses the classical concept of renal regeneration, i.e. stochastically surviving cells undergoing dedifferentiation (or epithelial-mesenchymal transition) followed by replenishment of the tubular epithelium. Furthermore however, this view has recently been challenged by the concept of organ-confined stem/progenitor cells, bone marrow-derived stem cells, or mesenchymal stem cells taking part in the regenerative events. Whereas results from animal models support the classical view, morphologically distinct cells have been demonstrated in human kidneys, requiring interpretation. This review presents some of the previous work and techniques and highlights issues that need to be reconciled.
In adult humans, the kidney tubules contain scattered cells with a distinct set of markers and properties, such as increased robustness during tubular damage. These cells may be induced by injury or represent a resident progenitor cell pool. To date, animal studies using lineage-tracing methods argue for an inductive scenario. In humans, the situation is less clear and one might speculate that the cellular heterogeneity might reflect elements of cellular reprogramming to a progenitor-like state, perhaps by induction. Due to intense investigational efforts, however, a scientific consensus may soon be reached, which will benefit further research.
急性肾损伤/肾衰竭最常见的肾内病因是肾小管损伤。肾小管呈细胞镶嵌状排列以履行其功能，在静息状态下，人体近五分之一的ATP消耗用于从滤液中重吸收物质，这使得尤其是近端肾小管对氧和/或营养物质剥夺高度敏感。肾小管上皮细胞通常处于有丝分裂静止状态，但若给予支持治疗，损伤后会表现出活跃的再生反应，从而实现功能恢复。尽管如此，再生能力背后的细胞机制仍未明确界定。这与皮肤和肠道等其他上皮组织不同，在这些组织中，干细胞从特定的微环境中持续产生新细胞。
本综述讨论了肾脏再生的经典概念，即随机存活的细胞经历去分化（或上皮-间质转化），随后补充肾小管上皮。然而，最近这一观点受到了器官内源性干/祖细胞、骨髓源性干细胞或间充质干细胞参与再生过程这一概念的挑战。虽然动物模型的结果支持经典观点，但在人类肾脏中已证实存在形态上不同的细胞，这需要进行解读。本综述介绍了一些先前的工作和技术，并强调了需要协调的问题。
在成年人体内，肾小管含有散在的细胞，这些细胞具有一组独特的标志物和特性，例如在肾小管损伤期间具有更强的耐受性。这些细胞可能是由损伤诱导产生的，或者代表一个常驻的祖细胞池。迄今为止，使用谱系追踪方法的动物研究支持诱导性情况。在人类中，情况尚不清楚，有人可能推测细胞异质性可能反映了细胞重编程为祖细胞样状态的某些因素，也许是通过诱导实现的。然而，由于大量的研究工作，可能很快会达成科学共识，这将有利于进一步的研究。
