Kinetics of transforming growth factor‐β1 and extracellular matrix in renal tubulointerstitial lesions of mercuric chloride‐treated Brown Norway rats

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Abstract
Renal tubulointerstitial lesions in mercuric chloride(HgCl2)‐treated Brown Norway rats were investigated focusing on the kinetics of transforming growth factor‐β1(TGF‐β1) and extracellular matrix (ECM). Rats were injected with 1 mg/kg b.w. of HgCl2 at days 0, 2, and 4, and 5 rats were killed at days 2, 4, 6, 8, 10, and 20, respectively. TGF‐β1 mRNA expression in the renal cortex measured by competitive RT‐PCR method reached a peak at day 6, mildly decreased at days 8 and 10, and increased again toward day 20. Signals of TGF‐β1 mRNA examined by in situ hybridization method were recognized in the regenerative tubular epithelium at day 6, and in both tubular epithelium and infiltrated mononuclear cells at day 20. After tubular injury, strong immunoreactivity to TGF‐β1 protein was found in desquamated tubular epithelial cells. Then, positive staining was found in the regenerative tubular epithelial cells. Later, infiltrated mononuclear cells also became positive for TGF‐β1 protein. In the ECM, deposition of fibronectin was prominent throughout the experimental period. In conclusion, this strongly suggests that TGF‐β1 derived from tubular epithelial cells and some macrophages might be related to the development of renal interstitial fibrosis in HgCl2‐treated BN rats.