Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
Kidney Int. 2010 Jun;77(11):950-5. doi: 10.1038/ki.2010.88. Epub 2010 Mar 24.
Transforming growth factor-beta (TGF-beta) is a cytokine known to participate in several processes related to the development of chronic kidney disease (CKD), including tubular degeneration. This is thought to occur mainly through apoptosis and epithelial-to-mesenchymal transition (EMT) of tubule epithelial cells, which give rise to a reduction of the tubular compartment and a scarring-like, fibrotic healing process of the interstitial compartment. In vivo blockade of TGF-beta action has been shown to reduce CKD-associated tubular damage. However, a direct action of TGF-beta on tubule cells is controversial as the underlying mechanism. On the one hand, TGF-beta is known to induce EMT of tubular cells, although its incidence in vivo can hardly explain the extent of the damage. On the other hand, a few publications have reported that TGF-beta induces a mild degree of apoptosis in cultured tubular cells. This most likely reflects the consequence of the cell-cycle arrest rather than a direct pro-apoptotic effect of TGF-beta. The implications of these observations are analyzed in the pathological context, where normal tubular cells do not normally proliferate, but they might divide for repair purposes. Furthermore, renal fibrosis, a TGF-beta-mediated event, is integrated as a potential, indirect effect contributing to tubule deletion.
转化生长因子-β（TGF-β）是一种细胞因子，已知参与慢性肾脏病（CKD）发展的几个过程，包括肾小管变性。这主要被认为是通过肾小管上皮细胞的细胞凋亡和上皮-间充质转化（EMT）发生的，导致肾小管腔减少和间质腔瘢痕样、纤维化的愈合过程。体内阻断 TGF-β的作用已被证明可减少 CKD 相关的肾小管损伤。然而，TGF-β对肾小管细胞的直接作用作为潜在机制仍存在争议。一方面，已知 TGF-β诱导肾小管细胞的 EMT，尽管其在体内的发生率很难解释损伤的程度。另一方面，一些出版物报道 TGF-β在培养的肾小管细胞中诱导轻度凋亡。这最可能反映了细胞周期停滞的结果，而不是 TGF-β的直接促凋亡作用。在病理环境中分析了这些观察结果的意义，在正常情况下，肾小管细胞不会增殖，但它们可能为了修复而分裂。此外，肾纤维化是 TGF-β介导的事件，被整合为潜在的、间接的导致肾小管缺失的效应。
