BACKGROUND: The aging kidney has a decreased ability to repair following injury. We have shown a loss in expression of α-catenin in the aging rat kidney and hypothesize that decreased α-catenin expression in tubular epithelial cells results in diminished repair capacity. METHODS: In an effort to elucidate alterations due to the loss of α-catenin, we generated NRK-52E cell lines with stable knockdown of α(E)-catenin. RESULTS: α(E)-catenin knockdown resulted in decreased wound repair due to alterations in cell migration. Analysis of gene expression in the α(E)-catenin knockdown cells demonstrated almost a complete loss of bone morphogenetic protein-7 (BMP-7) expression that was associated with decreased phospho-Smad1/5/8 staining. However, addition of exogenous BMP-7 increased phospho-Smad1/5/8, suggesting that the BMP-7 pathway remained intact in C2 cells. Given the potential role of BMP-7 in repair, we investigated its role in wound repair. Inhibition of BMP-7 decreased repair in non-targeted control cells; conversely, exogenous BMP-7 restored repair in α(E)-catenin knockdown cells to control levels. CONCLUSIONS: Taken together, the data suggests that the loss of α(E)-catenin expression and subsequent downregulation of BMP-7 is a mechanism underlying the altered migration of tubular epithelial cells that contributes to the inability of the aging kidney to repair following injury.
BACKGROUND: The aging kidney has a decreased ability to repair following injury. We have shown a loss in expression of α-catenin in the aging rat kidney and hypothesize that decreased α-catenin expression in tubular epithelial cells results in diminished repair capacity. METHODS: In an effort to elucidate alterations due to the loss of α-catenin, we generated NRK-52E cell lines with stable knockdown of α(E)-catenin. RESULTS: α(E)-catenin knockdown resulted in decreased wound repair due to alterations in cell migration. Analysis of gene expression in the α(E)-catenin knockdown cells demonstrated almost a complete loss of bone morphogenetic protein-7 (BMP-7) expression that was associated with decreased phospho-Smad1/5/8 staining. However, addition of exogenous BMP-7 increased phospho-Smad1/5/8, suggesting that the BMP-7 pathway remained intact in C2 cells. Given the potential role of BMP-7 in repair, we investigated its role in wound repair. Inhibition of BMP-7 decreased repair in non-targeted control cells; conversely, exogenous BMP-7 restored repair in α(E)-catenin knockdown cells to control levels. CONCLUSIONS: Taken together, the data suggests that the loss of α(E)-catenin expression and subsequent downregulation of BMP-7 is a mechanism underlying the altered migration of tubular epithelial cells that contributes to the inability of the aging kidney to repair following injury.
Authors: S Matsui; H Shiozaki; M Inoue; S Tamura; Y Doki; T Kadowaki; T Iwazawa; K Shimaya; A Nagafuchi; S Tsukita Journal: Virchows Arch Date: 1994 Impact factor: 4.064
Authors: Ki-Yoon Jung; Dana Dean; Jing Jiang; Susan Gaylor; William H Griffith; Robert C Burghardt; Alan R Parrish Journal: Mech Ageing Dev Date: 2004-06 Impact factor: 5.432
Authors: T Kadowaki; H Shiozaki; M Inoue; S Tamura; H Oka; Y Doki; K Iihara; S Matsui; T Iwazawa; A Nagafuchi Journal: Cancer Res Date: 1994-01-01 Impact factor: 12.701
Authors: Xinhui Wang; LaNita Nichols; Elizabeth A Grunz-Borgmann; Zhe Sun; Gerald A Meininger; Timothy L Domeier; Christopher P Baines; Alan R Parrish Journal: Toxicol Lett Date: 2016-12-15 Impact factor: 4.372