Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Kidney Blood Press Res. 2010;33(1):24-9. doi: 10.1159/000285844. Epub 2010 Feb 23.
Injured podocytes proliferate in cellular focal segmental glomerulosclerosis (FSGS), collapsing FSGS and crescentic glomerulonephritis, where TGF-beta(1) is overexpressed in hyperplastic podocytes. Yet effects of podocyte TGF-beta on podocyte growth and development of glomerulosclerosis have not been clearly defined. TGF-beta activates Smads, Ras/extracellular signal-regulated kinase (ERK) and phosphatidyl inositol-3-kinase (PI3K) pathways in podocytes, of which the major TGF-beta/Smad signaling pathway appears to override the minor TGF-beta-induced Ras/ERK/PI3K pathways. We provide evidence that increasedTGF-beta/Smad signaling activity by hyperplastic podocytes may lead to mesangial cell matrix overproduction and eventually to podocyte apoptosis and/or detachment, culminating in the development of glomerulosclerosis. In this regard, TGF-beta, which is overexpressed by hyperplastic podocytes, may play an important role for the cellular and collapsing variants of FSGS to evolve into the classic FSGS pattern. In contrast, podocyte proliferation that is induced by Ras/ERK signaling activity in proliferative podocyte diseases seems to be mostly independent of TGF-beta(1) activity. Collectively, these data bring new insights into our understanding of the overexpression of TGF-beta in hyperplastic podocytes in progressive glomerular diseases.
增生的足细胞在细胞性局灶节段性肾小球硬化症 (FSGS)、塌陷型 FSGS 和新月体性肾小球肾炎中增生，其中 TGF-β(1) 在增生的足细胞中过度表达。然而，足细胞 TGF-β 对足细胞生长和肾小球硬化症发展的影响尚未明确界定。TGF-β 在足细胞中激活 Smads、Ras/细胞外信号调节激酶 (ERK) 和磷脂酰肌醇-3-激酶 (PI3K) 途径，其中 TGF-β/Smad 主要信号通路似乎超过 TGF-β 诱导的 Ras/ERK/PI3K 次要途径。我们提供的证据表明，增生的足细胞中增加的 TGF-β/Smad 信号活性可能导致系膜细胞基质过度产生，并最终导致足细胞凋亡和/或脱落，导致肾小球硬化症的发展。在这方面，过度表达的 TGF-β 可能在增生性足细胞中发挥重要作用，使 FSGS 的细胞性和塌陷性变体演变为经典 FSGS 模式。相比之下，增生性足细胞中 Ras/ERK 信号活性诱导的足细胞增殖似乎在很大程度上独立于 TGF-β(1) 活性。总的来说，这些数据使我们对增生性足细胞中 TGF-β 过度表达在进行性肾小球疾病中的作用有了新的认识。
