Localisation and phenotypical characterisation of collagen-producing cells in TGF-beta 1-induced renal interstitial fibrosis.
Transforming growth factor beta 1 (TGF-beta 1) contributes to the accumulation of extracellular matrix (ECM) in the tubulointerstitial space in chronic renal diseases. Identification of target cells and the contribution of epithelial-mesenchymal transformation (EMT) in TGF-beta 1-induced fibrosis in vivo are currently under investigation. We have developed a transgenic model of slowly developing TGF-beta 1-driven tubulointerstitial fibrosis (TIF). By using this model our aim was to localise the ECM-producing cells, to investigate the temporal and spatial distribution of the cellular markers alpha-smooth muscle cell actin (alpha SM-actin), Fsp1 and Hsp47 and to explore the possible involvement of EMT in TGF-beta1-induced TIF in vivo. We utilised a combination of in situ hybridisation, immunohistochemistry and western blotting techniques and found that alpha SM-actin-positive interstitial cells are the main source of collagen types I and III and fibronectin, whereas collagen type IV(alpha 1/alpha 2) originates mainly from the tubular epithelial cells. Furthermore, macrophages are not important combatants during the early course of TGF-beta 1-induced TIF. Finally, EMT is not necessary for the initiation of TGF-beta 1-induced TIF. We conclude, that intervention directed against the recruitment of activated interstitial cells may avoid the development of end-stage renal disease.
Chai
Qing
Q
The Research Laboratory for Biochemical Pathology, The Institute for Experimental Clinical Research, Aarhus Kommunehospital, 44-Noerrebrogade, 8000 Aarhus C, Denmark.
Krag
Søren
S
Chai
Song
S
Ledet
Thomas
T
Wogensen
Lise
L
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D015415:Biomarkers; D005353:Fibronectins; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen