Sublethal injury leads to interstitial fibrosis and fibroblast activation after long-term 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding.

<p>(<b>A</b>) Plasma creatinine levels and urinary albumin/creatinine ratio in control (<i>white bar</i>) and DDC-fed mice (<i>black bar</i>) at days 7, 14, and 56. Data are presented as means ± SEM. *<i>P</i> < 0.05 compared with the control mice. Control and 7 days of DDC-fed mice samples were reproduced from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146871#pone.0146871.g001" target="_blank">Fig 1</a>; data were acquired using n ≥ 3 mice/group for the albumin/creatinine ratio. (<b>B</b>) Light and electron microscopic images of kidneys of control and DDC-fed mice at days 7, 14, and 56; top row, reticulin staining; middle row, Azan staining; bottom row, transmission electron microscopy (TEM); <i>red arrowheads</i>, accumulation of immature collagen fibers; <i>black asterisks</i>, accumulation of mature collagen fibers (blue staining); <i>arrows</i>, peritubular collagen fibers; <i>white asterisk</i>, myofibroblast with released collagen fibers. Scale bars = 25 μm (top row), 100 μm (middle row), and 2 μm (bottom row).