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Volume 83, Issue 6, Pages 1099-1108 (June 2013)
Cyst expansion and regression in a mouse model of polycystic kidney disease Hester Happé, Annemieke M. van der Wal, Daniela C.F. Salvatori, Wouter N. Leonhard, Martijn H. Breuning, Emile de Heer, Dorien J.M. Peters Kidney International Volume 83, Issue 6, Pages (June 2013) DOI: /ki Copyright © 2013 International Society of Nephrology Terms and Conditions
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Figure 1 Growth curves, 2KW/BW ratios, cystic indices, and blood urea levels in B6Ola-Pkd1nl,nl and wild-type mice. Body weight (g) for (a) males and (b) females are indicated in time (mean±s.e.m., n=2–7), (c) total kidney weight to body weight ratio (2KW/BW) and (d) total kidney weight (g) at different ages (median and interquertile range, IQR, n=2–7 per age), (e) cystic index (CI) represented as area-percentage (median and IQR, n=2–7 per age) and (f) blood urea concentration in time in mmol/l (mean±s.e.m., n=5–11 per age). Closed squares, B6Ola-Pkd1nl,nl mice; open diamonds, B6Ola-Pkd1wt,wt. Kidney International , DOI: ( /ki ) Copyright © 2013 International Society of Nephrology Terms and Conditions
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Figure 2 Histopathological characteristics of cystic kidneys inB6Ola-Pkd1nl,nlmice. (a–c) Periodic acid-Schiff staining showing progression of cystic disease in B6Ola-Pkd1nl,nl mice at 4, 8, and 24 weeks of age, respectively. (d–f) α-Smooth muscle actin (SMA) staining showing myofibroblasts and (g–i) Sirius Red staining for collagen as markers for fibrosis at 4 (d, g), 8 (e, h), and 24 (f, i) weeks of age. (j–l) Nephron-segment marker staining showing dilated tubules and cysts of proximal tubular origin at D7 as indicated by staining for megalin (j), and cysts of collecting duct origin at D14 (k) and D28 (l) as indicated by staining for aquaporin-2. (m, n) Clusters of inflammatory cells in cystic kidneys showing (m) leukocytes positive for CD45 staining and (n) mature macrophages as indicated by F4/80 staining. (o) Mature macrophages indicated by F4/80 staining and (p) alternatively activated macrophages stained for CD163 underlying cystic epithelia. (m–p) Twenty-four weeks of age. (q) Example of collapsing cysts at 24 weeks of age, Sirius Red staining. (r) Stretch of, and Ki-67-positive nuclei in cystic epithelium at 4 weeks of age. (s, t) Active caspase-3 staining showing apoptotic nuclei in cystic (s) and non-cystic epithelia (t) at 4 weeks of age. Asterisk indicates immune infiltrate filling the lumen of the remnant structure of a cyst. Arrows indicate F4/80-positive cells and CD163-positive cells (granular staining) underlying cystic epithelia. Closed arrowheads indicate examples of positive nuclei in epithelia, while open arrowheads indicate positive nuclei in interstitium. C, collapsing cyst; CD, cyst derived from collecting duct; DT, cyst of distal tubular origin; PT, cyst of proximal tubular origin. Kidney International , DOI: ( /ki ) Copyright © 2013 International Society of Nephrology Terms and Conditions
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Figure 3 Proliferation index and apoptotic index in time in B6Ola-Pkd1nl,nl and wild-type mice. (a) Proliferation index presented as percentage of Ki-67-positive nuclei over total nuclei. (b) Apoptotic index presented as percentage of active caspase-3-positive nuclei over total nuclei. Results are shown as mean±s.e.m. *P<0.05, **P<0.01. Kidney International , DOI: ( /ki ) Copyright © 2013 International Society of Nephrology Terms and Conditions
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Figure 4 Renal mRNA expression of genes involved in matrix remodeling at different ages. mRNA expression of (a) Serpine1 (PAI-1) (b) Mmp2, (c) Fn1(EDA), and (d) Col1a1 as analyzed by reverse transcriptase-multiplex ligation-dependent probe amplification. Expression was normalized to the housekeeping gene HPRT. Results are shown as median expression relative to the expression of wild-type mice at the age of 4 weeks, error bars represent interquartile range (n=2–5). Closed squares, B6Ola-Pkd1nl,nl mice; open diamonds, B6Ola-Pkd1wt,wt. The dotted line represents 2KW/BW, indicated on the right y-axis, showing pattern of renal volume in time. *P<0.05, **P<0.01, ***P< KW/BW, total kidney weight to body weight ratio. Kidney International , DOI: ( /ki ) Copyright © 2013 International Society of Nephrology Terms and Conditions
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Figure 5 Renal mRNA expression of potential biomarkers for autosomal-dominant polycystic kidney disease progression at different ages. mRNA expression of (a) Lcn2, (b) Sgp2, and (c) C3, as analyzed by reverse transcriptase-multiplex ligation-dependent probe amplification. Results are shown as median expression relative to the expression of wild-type mice at the age of 4 weeks; error bars represent interquartile range (n=2–5). Closed squares, B6Ola-Pkd1nl,nl mice; open diamonds, B6Ola-Pkd1wt,wt. The dotted line (in a and b) represents 2KW/BW, indicated on the right y-axis, showing pattern of renal volume in time.*P<0.05, **P<0.01, ***P<0.001. Kidney International , DOI: ( /ki ) Copyright © 2013 International Society of Nephrology Terms and Conditions
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