白细胞介素-18促肾小管上皮细胞转分化的机制研究

Intracellular signal transduction mechanism of interleukin - 18 promoting renal interstitial fibrosis

目的探讨白细胞介素-18（IL-18）诱导体外培养的人近端肾小管上皮细胞转分化的细胞内信号的转导机制。方法应用细胞培养技术培养HK-2细胞。予不同浓度的p38MAPK通路特异性阻断剂SB203580预孵育细胞30min后，再加入IL-18共同培养。应用RT—PCR方法检测α-SMA mRNA的表达水平，ELISA方法测定细胞胞浆中α—SMA的表达水平。结果SB203580可呈剂量依赖性地抑制IL—18诱导的HK-2细胞α-SMA基因和蛋白的表达。结论阻断p38MAPK信号通路可明显抑制IL—18诱导的HK-2细胞转分化作用：p38MAPK通路可能是调控IL-18诱导的HK-2细胞转分化的主要信号通路之一。

Objective To explore the intracellular signal transduction mechanism of transdifferentiation induced by IL - 18 in HK - 2 cells. Methods Human proximal tubular epithelial cell lines （HK -2 cells） were cultured in vitro. After preincubated with SB203580 for 30 minutes, cells were exposed to IL - 18 for 24, 48 and 72 hours respectively. The expression level of α - SMA mRNA in cul- tured HK- 2 cells were assessed by quantitative reverse transcription polymerase chain reaction （RT- PCR）. The expression level of α - SMA were measured by enzyme linked immunosorbent assay （ELISA）. Results IL - 18 - induced expression of α - SMA mRNA and protein were inhibited obviously by a dose - dependent manner when HK - 2 cells were incubated with SB203580. Conclusions IL - 18 -induced transdifferentiation of RTECs is suppressed obviously by blocking p38MAPK;IL - 18 - induced transdifferentiation of RTECs is probably mediated, at least in part, through the activation of p38MAPK and signaling pathways.