Intracellular processing of transforming growth factor-beta in mesangial cells.
Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional regulator of cell-growth, differentiation and extracellular matrix formation in several physiological conditions. It plays a crucial role in the process of glomerulosclerosis. Mature TGF-beta 1 is secreted as a latent form associated with the latency associated peptide (LAP), and its activation occurs through the LAP cleavage. The intracellular localization and the mechanisms of activation of TGF-beta 1 protein have not been elucidated in the mesangial cell. In the present report we examined the intracellular processing from TGF-beta 1 precursor to the latent-TGF-beta 1 in cultured mesangial cells by immunocytochemistry, using three rabbit polyclonal antibodies directed against different epitopes of human TGF-beta 1. The anti-LAP-TGF-beta 1 precursor Ab stained mesangial cells in the perinuclear region and in the cytoplasm in the area corresponding to the rough endoplasmic reticulum; the anti-COOH-terminal fragment of TGF-beta 1 Ab reacted in the same area, in vesicular structures located in the cytoplasm and furthermore, in the mesangial cell clusters, so-called hillocks, with an extracellular pattern; the anti-NH2-terminal fragment of TGF-beta 1 Ab stained only large exocytotic vesicles at the periphery of the cytoplasma. Our investigations suggest a conformational rearrangement of pro-TGF-beta 1 molecule occurring between the rough endoplasmic reticulum and the TGF-beta 1 secretion and support the idea that in mesangial cells the activation of TGF-beta 1 occurs during the secretion process. In conclusion, the processing of TGF-beta 1 in mesangial cells seems to be similar to that one observed in other mesenchymal cells.
Ceol
M
M
Institute of Internal Medicine, School of Medicine, University of Padua, Italy.
Vianello
D
D
Baggio
B
B
Meani
A
A
Schleicher
E
E
Anglani
F
F
Gambaro
G
G
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D011817:Rabbits; D013552:Swine; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D016212:Transforming Growth Factor beta