Tissue transglutaminase expression during neural differentiation of human mesenchymal stem cells.

Herein, we assessed the expression of transglutaminase-2 (TG2) during in vitroneural differentiation of human Mesenchymal Stem Cells (hMSCs) induced by someGrowth Factors (GFs). The amount and distribution of mRNAs for sometransglutaminase (TGs) isoforms (TG1, TG2, TG3, TG5) were also evaluated. Inaddition, we tested some neural lineage markers (Glial Acid Fibrillary Protein,GFAP; Neurofilament Protein, NF; Nestin; β-Tubulin III). A progressive increaseof all neural markers during GFs neural differentiation of hMSCs was found. Asignificant overexpression of TG1 and TG2 mRNA was observed in undifferentiatedhMSCs. GFs-treatment induced a progressive decrease of TG1 mRNA during hMSCsdifferentiation. A significant down-regulation of TG2 mRNA in 2 days in vitro(DIV) GFs-treated cells was observed. TG2 mRNA progressively increased during GFshMSCs differentiation, reaching after 6 DIV of GFs-treatment of similar values tothose observed in undifferentiated cells. TG3 mRNA levels were express at verylow only in undifferentiated hMSCs, whereas TG5 mRNA was undetectable inundifferentiated and differentiated hMSCs. Immunocytochemical and Western blotanalysis showed an overexpression of TG2 in undifferentiated hMSCs. A dramaticreduction of the protein levels in 2 DIV GFs-treated cells was observed. Itsexpression levels progressively increased during the differentiation of hMSCswith GFs, reaching after 6 DIV of the treatment similar values to those observed in undifferentiated cells. Our findings demonstrate the presence of multiple TGs in hMSCs during neural differentiation in vitro induced by GFs, and suggest that TG2 may be part of the downstream events associated to neural differentiation.