TGF-β3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: An in vivo study
Lui,Wing-Yee; Wong,Daria C.H.; Mruk,Dolores D.; Cheng,Chuen-yan
Endocrinology 144(4): 1139-1142
Publication date: 2003
Recent studies using Sertoli cells cultured in vitro to permittight junction (TJ) assembly have shown that TJ dynamics are regulated,at least in part, by TGF-ß3 via the p38 mitogen activated protein(MAP) kinase pathway. This in turn regulates the productionof occludin, a TJ-integral membrane protein, by Sertoli cells.Yet it is not known if this pathways is used by Sertoli cellsto regulate the blood-testis barrier (BTB) function in vivo.Using an in vivo model for studying BTB dynamics, we report hereinthe CdCl-induced BTB damage in rats was associated with a significantreduction in testicular occludin along with a loss of immunoreactiveoccludin in the seminiferous epithelium at the site of the BTB.Also, this CdCl-induced occludin loss from the BTB coincidedwith a surge in testicular TGF-ß3, as well as p-p38MAP kinase (the phosphorylated/activated form of p38), but notp38 MAP kinase and neither extracellular signal-regulated kinasenor its phosphorylated form (ERK/p-ERK), consistent with resultsof in vitro studies. More important, intratesticular administration ofSB202190, a specific p38 MAP kinase inhibitor, could block the CdCl-inducedoccludin loss from the BTB. These results illustrate that BTBdynamics in vivo are regulated by the TGF-ß3/p38 MAPkinase pathway, which in turn determines the level of occludinat the site of Sertoli cells TJs.