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TGF‐β1 impairs forskolin response through down‐regulation of CFTR in cultured vas deferens cells
Author(s) -
Yi Sheng,
Alves Fernando,
Schultz Bruce
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1042.21
Subject(s) - vas deferens , cystic fibrosis transmembrane conductance regulator , forskolin , cystic fibrosis , endocrinology , medicine , secretion , infertility , transforming growth factor , chemistry , biology , pregnancy , genetics , stimulation
Transforming growth factor β1 (TGF‐β1) is associated with infertility and is a modifier of cystic fibrosis severity, a disease that is associated with male infertility. Experiments were conducted to determine the impact of TGF‐β1 on vas deferens epithelial cells. PVD9902 cells, derived from pig vas deferens, were cultured for 14 days followed by exposure to TGF‐β1 or vehicle for 24 hr. Previous results showed that forskolin increases anion secretion via a cAMP pathway. TGF‐β1 attenuated forskolin‐stimulated anion secretion by >60%, although cAMP generation was reduced by only 20%. Semi‐quantitative RT‐PCR revealed that TGF‐β1 downregulates cystic fibrosis transmembrane conductance regulator (CFTR) mRNA abundance. Western blots revealed reduced levels for both fully glycosylated (C‐band) and core‐glycosylated CFTR (B‐band). Biotinylation indicated that TGF‐β1 decreased apical cell surface CFTR expression. These results suggest that TGF‐β1 causes a reduction in CFTR expression, which limits CFTR‐mediated anion secretion. Men harboring profound CFTR mutations exhibit infertility and reproductive duct anomalies, whereas mild mutations have variable presentations. Our results suggest that TGF‐β1 expression can reduce CFTR activity and thus would likely compound the effects associated with mild CFTR mutations (i.e., compromised CFTR expression or activity). [NIH HD058398 and RR017686.]