Heparin modulates proliferation and proteoglycan biosynthesis in murine mesangial cells: molecular clues for its activity in nephropathy.
Glycosaminoglycan administration has favourable effects on morphological and functional renal abnormalities in different models. The possibility that exogenous glycosaminoglycans modulate glomerular matrix synthesis was explored in both primary and SV40-MES13 murine mesangial cell cultures. On both cell types, both low-molecular-weight heparin and different glycosaminoglycans showed dose-dependent inhibition of proliferation and increase of 35SO4(2)-uptake. After 36 h the cell compartment contained a spectrum of 35S-molecules of less than 200 kDa; under heparin treatment, the two main 35SO4(2)-components (high and medium MW) increased by 16 and 37% respectively. Susceptibility to glycosidases revealed that heparin promotes the expression of heparan sulphate and increases that of chondroitin sulphate. Moreover, heparin modifies the expression of decorin and biglycan, involved in adhesion and fibrillogenesis, while not affecting perlecan. The extracellular matrix modulation in renal cells, for which the sulphation type and ratio of heparin are crucial, may thus explain the beneficial renal effects of heparin.
Caenazzo
C
C
Institute of Histology, University Medical School of Padova, Italy.
Garbisa
S
S
Ceol
M
M
Baggio
B
B
Borsatti
A
A
Marchi
E
E
Gambaro
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000096:biosynthesis; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis*; D013431:Sulfates / Q000378:metabolism
D002809:Chondroitin Sulfates; D003598:Cytoskeletal Proteins; D004247:DNA; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate; D011509:Proteoglycans; D013431:Sulfates