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Interstitial myofibroblasts in experimental renal infection and scarring
T D Hewitson1, H L Wu, G J Becker
1Department of Nephrology, Royal Melbourne Hospital, Vic., Australia.
Abstract:
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)
Insights
Myofibroblasts transiently accumulate during experimental kidney infection, with their numbers peaking early and then declining. These cells, identified by alpha-smooth muscle actin, proliferate locally and contribute to renal interstitial fibrosis.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Myofibroblast-like cells possess features of both fibroblasts and smooth muscle cells.
- Understanding their role in renal infection and fibrosis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the temporal and spatial distribution of myofibroblast-like cells in a rat model of experimental renal infection.
- To determine the origin and contribution of myofibroblasts to renal interstitial fibrosis.
Main Methods:
- Induction of renal infection in Sprague-Dawley rats using Escherichia coli.
- Identification of myofibroblasts via morphology and immunohistochemistry for alpha-smooth muscle actin (alpha-SMA).
- Assessment of cell proliferation (bromodeoxyuridine incorporation), monocyte presence (ED-1 staining), and collagen III deposition.
Main Results:
- Interstitial alpha-SMA staining, indicative of myofibroblasts, increased significantly by day 3 post-infection and then decreased by day 24.
- Bromodeoxyuridine incorporation in myofibroblasts peaked at day 3, suggesting local proliferation.
- Monocyte numbers and collagen III deposition also increased during the infection, with collagen III remaining elevated at day 24.
Conclusions:
- Myofibroblasts transiently accumulate in the renal interstitium during experimental infection.
- These myofibroblasts are, at least in part, derived from local proliferation.
- The transient accumulation of myofibroblasts is associated with renal interstitial fibrosis.