Tubular cell senescence and expression of TGF-β1 and p21WAF1/CIP1 in tubulointerstitial fibrosis of aging rats
Tubular cell senescence and expression of TGF-β1 and p21WAF1/CIP1 in tubulointerstitial fibrosis of aging rats
复制标题
DOI：
10.1006/exmp.2000.2346
复制
发表时间：
2001-02-01
影响因子：
3.6
通讯作者：
Singhal, PC
中科院分区：
文献类型：
--
作者：
Ding, GH;Franki, N;Singhal, PC
肾脏老化被认为是肾功能受损和肾小管间质和肾小球结构改变的慢性过程。细胞衰老与细胞结构和功能的改变有关，包括细胞因子的表达以及细胞外基质蛋白的结构和调节成分。在这项研究中，我们验证了衰老肾细胞可能随着年龄的增长而在体内积累的假设。我们还评估了衰老肾脏中转化生长因子(TGF)- β 1和p21（WAF1/CIP1）的表达。本研究选用3、12、24月龄的Sprague-Dawley大鼠。处理肾组织进行形态计量学和衰老分析。通过Northern或Western blot分析和免疫组织化学检测tgf - β 1和p21（WAF/CIP1）的表达。在12个月大时发生实质性的小管间质损伤，但在24个月大时观察到明显的肾小球结构改变。β -半乳糖苷酶染色检测小管细胞衰老。随着年龄的增长，这种染色的频率和强度增加。肾皮质tgf - β 1 mRNA表达和p21（WAF1/CIP1）蛋白水平显著升高。tgf - β 1和p21（WAF1/CIP1）的表达增强局限于小管间质细胞。这些数据表明，小管细胞经历衰老并表达增加的tgf - β 1和p21（WAF1/CIP1）。随着年龄的增长。这些与年龄相关的细胞和分子改变可能在衰老过程中小管间质纤维化和肾小球硬化的发生和/或进展中起重要作用。(C) 2001学术出版社。
Kidney aging has been recognized as a chronic process of compromised renal function and structural changes in the tubulointerstitium and glomerulus. Cell senescence is associated with alterations in cell structure and function, including expression of cytokines and structural and regulatory components of extracellular matrix proteins. In this investigation, we tested the hypothesis that senescent renal cells may accumulate in vivo with advancing age. We also evaluated the expression of transforming growth factor (TGF)-beta1 and p21(WAF1/CIP1) in aging kidneys. Sprague-Dawley rats at the ages of 3, 12, and 24 months were used for this study. Renal tissues were processed for morphometric and senescence analysis. Expression of TGF-beta1 and p21(WAF/CIP1) was evaluated by Northern or Western blot analysis and immunohistochemistry. Substantial tubulointerstitial injury occurred at the age of 12 months, but significant glomerular structure alteration was observed at the age of 24 months. Tubular cells developed senescence, which was detected by beta -galactosidase staining. This staining increased in frequency and intensity with age. Renal cortices showed a significant increase in the mRNA expression for TGF-beta1 and protein level for p21(WAF1/CIP1). The enhanced expression of TGF-beta1 and p21(WAF1/CIP1) was localized in the tubulointersititial cells. These data suggest that tubular cells undergo senescence and express increased TGF-beta1 and p21(WAF1/CIP1). With advancing age. These age-related cellular and molecular alterations may play an important role in the initiation and/or progression of tubulointerstitial fibrosis and glomerulosclerosis in aging. (C) 2001 Academic Press.