[Expression of endothelin 1 and tumor necrosis factor alpha in injuried renal tubules and their influences on renal interstitial fibroblasts].
OBJECTIVE
To study the expression of endothelin 1 (ET-1) and tumor necrosis factor (TNFalpha) in the epithelial cells of normal and injured renal tubules and their influences on renal interstitial fibroblasts.


METHODS
Cultivation of renal tubular epithelial cells and renal interstitial fibroblasts and establishment of a renal tubulo-interstitial fibrosis (TIF) animal model; reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining, radioimmunoassay (RIA), double immunohistochemical; and (3)H-TDR incorporation techniques were applied to study the relationship between ET-1, plus TNFalpha and the proliferation of renal interstitial fibroblasts.


RESULTS
Expression of ET-1 mRNA and TNFalpha mRNA from renal tubular epithelial cells was obtained (546 bp and 415 bp) respectively as well as the relevant ET-1 and TNFalpha proteins. The concentration of ET-1 and TNFalpha in the culture medium were 1.42 pg/ml and 0.58 ng/ml respectively. The amount of ET-1 and TNFalpha was increased during cell injury and regeneration. In addition, the ratio of (3)H-TDR incorporation and the expression of ET-R mRNA and TNF-R1 mRNA (545 bp and 347 bp) were markedly increased than that of the control group (P < 0.05) when ET-1 or TNFalpha was added in the culture media.


CONCLUSIONS
Injured and regenerated renal tubular epithelial cells are able to synthesize and liberate more ET-1 and TNFalpha than that of the normal renal tubules. ET-1 and TNFalpha are also effective in promoting the proliferation of renal interstitial fibroblasts through ET-R and TNF-R.
Li
L
L
Department of Pathology, Beijing Medical University, Beijing 100083.
Zou
W
W
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000032:analysis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D015870:Gene Expression; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D015703:Antigens, CD; D019332:Endothelin-1; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha