Weissgarten J, Modai D, Berman S, Cohn M, Galperin E, Averbukh Z
Nephrology Division, Assaf Harofeh Medical Center, Zerifin, Israel.
Nephron. 2000 Jul;85(3):248-53. doi: 10.1159/000045668.
While the bulk of renal hypertrophy induced by contralateral nephrectomy or a high-protein diet consists of tubular cell growth, there is some evidence suggesting that mesangial cells play a role in this phenomenon. Previous data suggest that this role of mesangial cells is associated with their proliferation. We, therefore, undertook this investigation to assess the proliferative responses of mesangial cells, originating from single remaining kidneys or from kidneys of rats fed a high-protein diet, to epinephrine, endothelin, arginine vasopressin, neo-synephrine, or epidermal growth factor (EGF). All agents significantly enhanced the proliferation of normal mesangial cells, though the responses to neo-synephrine and EGF were significantly lower as compared with the other growth promoters. The mitogenic effects of the first three agents on single kidney mesangial cells were significant, but blunted as compared with control cells. This blunting was not evident in the case of the latter two mitogens. A significant enhancement of proliferation of mesangial cells originating from protein-fed rats was produced by epinephrine, neo-synephrine, and EGF. These effects were statistically not different from those observed in normal mesangial cells. The proliferative response to each of the mitogens used in the study proved highly specific for each mitogen, since it was abolished by respective specific inhibitors. Mesangial cells may play a role in the activation and later in progressive inhibition of renal hypertrophy in vivo.
虽然对侧肾切除或高蛋白饮食诱导的肾肥大主要由肾小管细胞生长构成,但有证据表明系膜细胞在这一现象中发挥作用。先前的数据表明系膜细胞的这一作用与其增殖有关。因此,我们开展了这项研究,以评估源自单肾留存大鼠或高蛋白饮食喂养大鼠肾脏的系膜细胞对肾上腺素、内皮素、精氨酸加压素、新福林或表皮生长因子(EGF)的增殖反应。所有药物均显著增强了正常系膜细胞的增殖,不过与其他生长促进剂相比,对新福林和EGF的反应显著更低。前三种药物对单肾系膜细胞的促有丝分裂作用显著,但与对照细胞相比有所减弱。后两种有丝分裂原的情况则未出现这种减弱。肾上腺素、新福林和EGF显著增强了高蛋白饮食喂养大鼠来源的系膜细胞的增殖。这些作用在统计学上与正常系膜细胞中观察到的作用并无差异。研究中使用的每种有丝分裂原的增殖反应对每种有丝分裂原均具有高度特异性,因为其被各自的特异性抑制剂所消除。系膜细胞可能在体内肾肥大的激活及随后的渐进性抑制中发挥作用。