Modulation of cell proliferation and hypertrophy by gangliosides in cultured human glomerular mesangial cells.
Glomerular mesangial cells (GMCs) in diverse renal diseases undergo cell proliferation and/or hypertrophy, and gangliosides have been reported to play an important role in modulating cell structure and function. This study compared the effects of transforming growth factor-beta1 (TGF-beta1) and the effects of the application of exogenous gangliosides on GMCs and investigated whether the application of exogenous gangliosides regulated cellular proliferation and hypertrophy. Human GMCs were cultured with exogenous gangliosides and TGF-beta1 in a media containing 10% fetal bovine serum and in a media without the fetal bovine serum. Exogenous gangliosides biphasically changed the proliferation of human GMCs (0.1-1.0 mg/mL). A low concentration (0.1 mg/mL) of gangliosides mainly increased the number of human GMCs, whereas cellular proliferation was significantly reduced by raising the concentration of exogenous gangliosides. TGF-beta1 greatly reduced the number of human GMCs in a concentration-dependent manner (1-10 ng/mL). Serum deprivation accelerated the gangliosides- and TGF-beta1-induced inhibition of mesangial cell proliferation to a greater extent. Gangliosides (1.0 mg/ mL) and TGF-beta1 (10 ng/mL) both caused a significant increase in the incorporation of [3H]leucine per cell in the serum-deprived condition, whereas it was completely reversed in serum-supplemented condition. Similar results to the [3H]leucine incorporation were also observed in the changes in cell size measured by flow cytometric analysis. These results show that exogenous gangliosides modulate cell proliferation and hypertrophy in cultured human GMCs, and these cellular responses were regulated differently based on whether the media contained serum or not. Results from the present study raise new possibilities about the potential involvement of gangliosides in the development of mesangial cell proliferation and hypertrophy.
Lee
Seoul
S
Department of Pharmacology, Wonkwang University School of Medicine, 334-2 Shinyongdong, Iksan, Jeonbuk 570-749, Korea.
Ahn
Seon Ho
SH
Baek
Seung Hoon
SH
Song
Ju Hung
JH
Choo
Young Kug
YK
Kwon
Oh Deog
OD
Choi
Bong Kyu
BK
Jung
Kyu Yong
KY
D000818:Animals; D001923:Brain Chemistry; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005732:Gangliosides / Q000302:isolation & purification / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D006801:Humans; D006984:Hypertrophy; D007930:Leucine / Q000032:analysis; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005732:Gangliosides; D016212:Transforming Growth Factor beta; D007930:Leucine