Interstitial myofibroblasts in experimental renal infection and scarring.
We have examined the temporal and spatial distribution of myofibroblast-like cells, a phenotype with fibroblast and smooth muscle features, in an experimental model of renal infection. Escherichia coli organisms (10(5)) were inoculated directly into the renal cortex of Sprague-Dawley rats weighing 270 g. Saline was substituted in a control group. The animals were sacrificed at five time points up to day 24 (E. coli n = 8, controls n = 3 each interval). Myofibroblasts were identified by morphology and immunohistochemistry for alpha smooth muscle actin (alpha-SMA) and compared with staining for monocytes (ED-1), collagen III, and bromodeoxyuridine incorporation. Histological changes included a focal lesion in E. coli infected animals. Interstitial alpha-SMA staining was confined to spindle-shaped cells resembling myofibroblasts. The percent fractional area of alpha-SMA staining in the lesion increased from 0.12 +/- 0.09 at day 1 to 20.0 +/- 7.1 at day 3 (p < 0.005), decreasing progressively to 2.0 +/- 2.6 by day 24. This paralleled bromodeoxyuridine incorporation in myofibroblasts: 0.4 +/- 0.5 cells/0.25 mm2 at day 1, 105.0 +/- 36.3 at day 3, and 2.6 +/- 2.2 cells/0.25 mm2 at day 24. ED-1-positive cells increased from 374 +/- 200/0.25 mm2 at day 1 to 894 +/- 88 at day 3 (p < 0.01), declining to 230 +/- 108/0.25 mm2 by day 24. Intracellular collagen III and alpha-SMA stainings were colocalized at day 3. The fractional area of collagen III increased by day 24 (p < 0.05). In conclusion, myofibroblasts accumulate transiently during renal interstitial fibrosis and are derived at least in part from local proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hewitson
T D
TD
Department of Nephrology, Royal Melbourne Hospital, Vic., Australia.
Wu
H L
HL
Becker
G J
GJ
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology*; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D003094:Collagen