ANALYSIS OF REGULATORY MECHANISM OF VIATAMIN D IN THE GROWTH AND DIFFERENTIATION OF EPIDERMAL KERATINOCYTES

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WE EXAMINED THE EFFECT OF VITAMIN D_3 ON THE CELL CYCLE OF EPIDERMAL KERATINOCYTES.VITAMIN D3 INDUCED THE GROWTH ARREST MAINLY IN G1/GO PHASE ALTHOUGH IT ARRESTS THE KERATINOCYTE GROWTH PARTIALLY IN M PHASE.THE EFFECT OF VITAMIN D3 ON THE KERATINOCYTE DIFFERENTIATION WAS EXAMINED BY MEASURING THE NUMBER OF INVOLUCRIN-POSITIVE CELLS USING ANTI-INVOLUCRIN ANTIBODY AND FLOWCYTOMETRY.VITAMIN D_3 AT 10^<-6> M INCREASED THE INVOLUCRIN-POSITIVE CELLS.THIS INDICATES THAT VITAMIN D_3 INDUCED THE KERATINOCYTE DIFFERENTIATION.RETINOBLASTOMA GENE WAS IDENTIFIED AS TUMOR SUPPRESSOR GENE ORIGINALLY.LATER, IT WAS SHOWN THA RETINOBLASTOMA GENE PRODUCT (PRB) REGULATES THE CELL CYLCE BY MODULATING THE TRANSITION FROM G1/G0 TO S PHASE.NAMELY, PHOSPHORYLATION OF PRB INTIATES THE TRANSITION FROM G1/G0 TO S PHASE.THEREFORE, WE STUDIED THE INBOLBEMENT OF PRB IN THE GROWTH INHIBITORY MECHANISM OF HUAMAM KERATINOCYTES BY VITAMIN D_3. PRB WERE VISUALIZED THE DIFFERENCE OF MOLECULAR WEIGHT AND QUANTITATED BY DENSITOMETER.THE ADDITION OF 10^<-6> M VITAMIN D_3 INCREASED THE DEPHOSPHORYLATED PRB IN A TIME DEPENDENT MANNER FROM 23% AT 0 H TO 58% AT 48 H.THUS, THE INCREASE OF DEPHOSPHORYLATED PRB WAS CLOSELY RELATED TO THE GROWTH INHIBITION OF HUMAN KERATINOCYTES BY VITAMIN D_3. WE COMPARED THE GROWTH INHIBITORY EFFECT OF VITAMIN D_3 ON NORMAL AND SV40 TRANSFORMED HUMAN KERATINOCYTES.VITAMIN D_3 AT 10^<-6> M INHIBITED THE GROUTH OF NORMAL HUMAN KERATINOCYTES BY MORE THAN 95%. IN CONTRAST, THE GROWTH OF TRANSFORMED HUMAN KERATINOCYTES WAS REDUCED ONLY BY 50%. SINCE THE GROWTH INHIBITION OF HUMAN KERATINOCYTES BY TGF-beta WAS ABOLISHED IN SV40-TRANSFORMED KERATINOCYTES PROBABLY THROUGH THE BINDING OF LARGE T ANTIGEN TO PRB, THE POSSIBLE INVOLVEMENT OF TGF-beta IN THE GROWTH INHIBITORY MECHANISM BY VITAMIN D_3 WAS SUGGESTED.