Nowak G, Schnellmann R G
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Toxicol Appl Pharmacol. 1997 Jul;145(1):175-83. doi: 10.1006/taap.1997.8166.
Renal proximal tubular cell (RPTC) monolayers exposed to the model oxidant tert-butylhydroperoxide (TBHP; 0.8 mM) for 1.5 hrs were 33 and 31% confluent after 1 and 4 days, respectively. Control monolayers remained 100% confluent throughout the experiment. Exogenous TGF-beta1 promoted monolayer deterioration by potentiating cellular death and suppressed EGF-stimulated regeneration of the RPTC monolayer. Net TGF-beta1 production in injured RPTC increased 1.7- and 3.2-fold on Days 1 and 2, respectively, and returned to control levels 4 days following TBHP treatment. An anti-TGF-beta antibody increased monolayer confluence to 50% and DNA content 1.3-fold 4 days after TBHP exposure. L-Ascorbic acid 2-phosphate (AscP) present only during the recovery period increased monolayer confluence to 67% but had no effect on RPTC proliferation, suggesting that AscP promoted monolayer regeneration by cellular migration/spreading. AscP present continuously had no effect on the extent of TBHP-induced injury but promoted regeneration of RPTC with increased monolayer confluence (1.8-fold) and DNA content (1.8-fold) and decreased cellular lysis by 52% 4 days following TBHP exposure. The results demonstrate that TBHP-induced injury increases net TGF-beta1 production in RPTC and that autocrine TGF-beta1 inhibits regeneration of the monolayer by potentiating cellular injury and monolayer deterioration. The data also show that AscP is not cytoprotective during TBHP exposure but promotes RPTC regeneration by stimulating proliferation and migration/spreading and decreasing cellular death during the recovery period.
将肾近端小管细胞（RPTC）单层暴露于模型氧化剂叔丁基过氧化氢（TBHP；0.8 mM）1.5小时后，分别在1天和4天后汇合度为33%和31%。对照单层在整个实验过程中保持100%汇合。外源性转化生长因子β1（TGF-β1）通过增强细胞死亡促进单层退化，并抑制表皮生长因子（EGF）刺激的RPTC单层再生。损伤的RPTC中TGF-β1的净产生在第1天和第2天分别增加了1.7倍和3.2倍，并在TBHP处理后4天恢复到对照水平。抗TGF-β抗体在TBHP暴露4天后将单层汇合度提高到50%，DNA含量提高了1.3倍。仅在恢复期存在的L-抗坏血酸2-磷酸酯（AscP）将单层汇合度提高到67%，但对RPTC增殖没有影响，表明AscP通过细胞迁移/铺展促进单层再生。持续存在的AscP对TBHP诱导的损伤程度没有影响，但促进了RPTC的再生，使单层汇合度（1.8倍）和DNA含量（1.8倍）增加，并在TBHP暴露4天后使细胞裂解减少52%。结果表明，TBHP诱导的损伤增加了RPTC中TGF-β1的净产生，自分泌的TGF-β1通过增强细胞损伤和单层退化抑制单层再生。数据还表明，AscP在TBHP暴露期间没有细胞保护作用，但在恢复期通过刺激增殖、迁移/铺展和减少细胞死亡促进RPTC再生。
