TGF-β3 regulates the blood-testis barrier dynamics via the p38 mitogen activated protein (MAP) kinase pathway: An in vivo study

Document Type

Article (peer-reviewed)

Publication Date

2003

Abstract

Recent studies using Sertoli cells cultured tn vitro to permit tight junction (TJ) assembly have shown that TJ dynamics are regulated, at least in part, by TGF-β3 via the p38 mitogen activated protein (MAP) kinase pathway. This in turn regulates the production of occludin, a TJ-integral membrane protein, by Sertoli cells. Yet it is not known if this pathway is used by Sertoli cells to regulate the blood-testis barrier (BTB) function in vivo. Using an in vivo model for studying BTB dynamics, we report herein the CdCl2-induced BTB damage in rats was associated with a significant reduction in testieular oceludin along with a loss of immunoreaetive oeeludin in the seminiferous epithelium at the site of the BTB. Also, this CdCl2-induced occludin loss from the BTB coincided with a surge in testicular TGF-β3, as well as p-p38 MAP kinase (the phosphorylated/activated form of p38), but not p38 MAP kinase and neither extracellular signal-regulated kinase nor its phosphorylated form (ERK/p-ERK), consistent with results of in vitro studies. More important, intratesticular administration of SB202190, a specific p38 MAP kinase inhibitor, could block the CdCl2-induced occludin loss from the BTB. These results illustrate that BTB dynamics in vivo are regulated by the TGF-β3/p38 MAP kinase pathway, which in turn determines the level of occludin at the site of Sertoli cell TJs.

DOI

10.1210/en.2002-0211

Language

English

https://doi.org/10.1210/en.2002-0211

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