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α (E)‐catenin regulates Bmp7 in tubular epithelial cells (691.3)
Author(s) -
Nichols LaNita,
Ślusarz Anna,
GrunzBorgmann Elizabeth,
Parrish Alan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.691.3
Subject(s) - bone morphogenetic protein 7 , gene knockdown , microbiology and biotechnology , catenin , wound healing , cell culture , cell , cytoplasm , cell growth , bone morphogenetic protein , signal transduction , wnt signaling pathway , biology , cancer research , chemistry , medicine , immunology , biochemistry , gene , genetics
Acute kidney injury (AKI) most often occurs in a background of chronic kidney disease, both of which increase with age. Several studies have shown increased incidence and severity of AKI in aged patients. Previously, our laboratory has shown that aging is associated with a loss of α‐catenin expression in rat proximal tubular epithelium. To understand the consequences of reduced α‐catenin expression, stable α (E)‐catenin knockdown (C2) and non‐targeted control (NT3) cell lines were generated in the NRK‐52E rat proximal tubular epithelial cell line. C2 cells are marked by a significant decrease in wound repair due to alterations in cell migration. Interestingly, expression of a bone morphogenic protein, Bmp7 is significantly reduced in C2 cells. The loss of Bmp7 expression is also associated with alterations in downstream signaling. In NT3 cells, a strong nuclear staining of phospho‐Smad1/5/8 is seen, while a diffuse cytoplasmic signal is seen in C2 cells. However, shortly after addition of exogenous Bmp7, C2 cells display a similar nuclear localization as control. We then examined the role of Bmp7 in repair. Addition of exogenous Bmp7 to C2 cells rescued wound healing to levels comparable to control NT3 cells. Conversely, a Bmp7 antagonist, LDN193189, inhibits wound healing in NT3. Taken together, these results demonstrate that α‐catenin plays a role in the regulation of Bmp7. Grant Funding Source : supported by NIH RO1AAG034154