The pluripotent cytokine pleiotrophin is induced by wounding in human mesangial cells.
Mesangial re-modeling and mesangial cell (MC) migration are features of several glomerular diseases including mesangiocapillary glomerulonephritis. In vitro investigations have recently identified ADAM-15, a multidomain adamalysin, as central to the migration of MC. The current study used array technology to investigate the expression of other genes in migrating cells and identified pleiotrophin (PTN), platelet-derived growth factor alpha polypeptide chain, colony stimulating factor, and four members of the tumor necrosis factor-alpha superfamily as major genes that were upregulated. Transcriptional induction of PTN was confirmed by reverse transcription-polymerase chain reaction and Northern blotting and induction of the protein by Western blotting and immunohistochemical localization. PTN was observed associated with mesangial 'hillocks' in confluent MC cultures. In contrast, in models of migration, migrating cells had the highest expression of cell-associated PTN. PTN protein was less evident, however, in the conditioned medium of MCs. Treatment of MC with heparanase removed PTN from the cells suggesting that its localization was owing to an association with heparan sulfates on the cell surface or in the extracellular matrix. This is the first description of the expression of PTN by human MCs and the data suggest that it is rapidly induced in cells that are triggered to migrate. The result of this induction is currently under investigation.
Martin
J
J
Institute of Nephrology, Cardiff University, Heath Park, Cardiff, Wales, UK. martinj1@cf.ac.uk
Bowen
T
T
Steadman
R
R
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008666:Metalloendopeptidases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D003115:Colony-Stimulating Factors; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; C066845:pleiotrophin; D008666:Metalloendopeptidases; C028220:Crotalus adamanteus proteinase II; D011133:Polysaccharide-Lyases; C083872:heparatinase I; C083873:heparatinase II