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. Author manuscript; available in PMC: 2016 Sep 16.
Published in final edited form as: JCI Insight. 2016 Aug 18;1(13):e87023. doi: 10.1172/jci.insight.87023

Figure 1. Global targeting of ADAM17 results in similar initial IRI-induced injury but in reduced IRI-induced fibrosis.

Figure 1

ADAM17ex/ex mice and their WT littermates were subjected to bilateral ischemia for 30 minutes followed by reperfusion. (A and B) Time-course of changes in serum creatinine and BUN (n = 6–15 per time point). (C) Time-course of urinary KIM1 levels over time measured by ELISA (n = 5–10 per time point). (D) Tubular damage was scored in kidney cortex at day 1 after ischemia (n = 6–7). (E) Time course of cortical CD31+ area quantified after immunostaining (n = 4). (F) The induction of fibronectin and αSMA in kidney cortex was examined by immunostaining 21 days after injury (top: representative images; bottom: quantification, n = 6; scale bar: 50 μm). (G) Fibronectin protein expression at day 21 after injury was examined by Western blot (left: sample blots; right: quantification; GAPDH was used as loading control; n = 5). (H and I) Masson’s trichrome staining at day 21 after injury in kidney cortex (H: representative images; I: quantification; n = 6; scale bar: 100 μm). (J) Total interstitial area (n = 6) and (K) dilated tubules were quantified at day 21 after injury (n = 6). (L) Soluble TNFα was measured by ELISA in control (WT/WT), hypomorphic (ex/ex), and WT mice injected with recombinant ADAM17 prodomain (WT/WT+A17pro) 2 days after injury (n = 4). (M) The induction of fibronectin and αSMA was examined in kidney cortex by immunostaining in vehicle or ADAM17 prodomain inhibitor–injected WT mice 5 days after injury (left: representative images, right: quantification; n = 4; scale bar: 50 μm). *P < 0.05; **P < 0.01; ***P < 0.001 as determined by an unpaired 2-tailed Student’s t test. Diamond symbol denotes position of kidney capsule. ADAM17, a disintegrin and metalloprotease 17; BUN, blood urea nitrogen; IRI, ischemia reperfusion injury; KIM1, kidney injury molecule 1; MT, Masson’s trichrome; αSMA, alpha smooth muscle actin; TNFα, tumor necrosis factor alpha; WB, Western blot.