*4.3. GJs, Cx43, and Cx26 as Molecular Candidate Targets of the Potential Anti-fibrotic Action of PRP*

Another main finding of this study is the compelling experimental evidence indicating, for the first time, that GJs and Cx43 are molecular candidate targets of the potential anti-fibrotic action of PRP. Indeed, PRP treatment affected the occurrence of voltage-dependent Ij, which was reduced at 48 h and even abolished after 72 h of culture; concomitantly, it prevented the TGF-β1 induced increase of Cx43 expression. Interestingly, the cells induced to differentiate in the presence of PRP mostly exhibited scarcely/not voltage-dependent Ij along with an observed upregulation of Cx26, especially after 48 h. We may suppose that these events reflect a compensatory mechanism to maintain a sort of cell-to-cell communication, upon PRP treatment. In addition, we may speculate a major role of Cx26 in this condition that may be linked to the ability of this Cx type to form hemichannels rather than highly regulated GJs. We should point out the ability of hemichannels themselves to act as membrane channels able to mediate cell communication with surrounding extracellular environment: recent studies confirm a link between hemichannel-mediated ATP release and the progression and development of fibrosis in different tissue types [95–98]. In this line, the role of Cx26 in forming scarcely voltage-dependent GJs and/or hemichannels and the possible relation with ATP content in our cell model is an interesting topic deserving further investigation.
