Transforming growth factor-beta 1 inhibits enkephalinase (EC 3.4.24.11) gene expression in human endometrial stromal cells and sex skin fibroblasts in culture.

Abstract

This study was conducted to evaluate the negative regulation of enkephalinase by an endogenously produced peptide, namely transforming growth factor-beta 1 (TGF beta 1). We found that TGF beta 1 acts in human endometrial stromal cells and sex skin fibroblasts in culture to cause a striking decrease (60% to > 90% in 3-7 days) in the specific activity of enkephalinase (membrane metalloendopeptidase; EC 3.4.24.11) by reducing the levels of enkephalinase mRNA and protein. Platelet-derived growth factor caused a slight reduction in enkephalinase specific activity in endometrial stromal cells; epidermal growth factor caused a slight decrease in enkephalinase specific activity in sex skin fibroblasts. In studies in which TGF beta 1 treatment and [35S]methionine labeling were conducted simultaneously, radiolabeling of enkephalinase was decreased. When proteins were radiolabeled with [35S] methionine before treatment with TGF beta 1, the extent of enkephalinase radiolabeling was similar to that in nontreated cells. These findings are indicative that TGF beta 1 acts to decrease enkephalinase activity by a reduction in gene transcription or mRNA stability and not by accelerated degradation of enkephalinase protein.

Expression of neutral endopeptidase (NEP/CD10) on pancreatic tumor cell lines, pancreatitis and pancreatic tumor tissues

“…The expression of NEP/CD10 protein was slightly upregulated after stimulation with EGF which is in contrast to renal vascular smooth muscle cells where NEP/CD10 mRNA expression was reduced after stimulation with EGF 36. The cytokine TGF‐β did not influence the NEP/CD10 expression in PATU‐8988T, HUP‐T3 and HUP‐T4 cells, whereas in human endometrial stromal cells an approximately 60% reduced NEP/CD10 expression was detectable upon 3 days of TGF‐β treatment 37. These results are again controversial to renal vascular smooth muscle cells in which TGF‐β was found to upregulate NEP/CD10 expression 36.…”

Human Parturition: Distinction Between the Initiation of Parturition and the Onset of Labor

“…47 This rapid decline in enkephalinase activity may be caused by the action of TGF-β, which is expressed in late secretory endometrium 48 and is effective in decreasing enkephalinase in stromal cells in culture. 49 Thus, TGF-β may act to negate, even actively oppose, the action of progesterone on enkephalinase activity in endometrium. Other non steroidal, endogenously produced agents also may function as antiprogestins; such an antiprogestin may be a steroid if it was active by way of a mecha nism independent of the progesterone receptor, e.g., via an orphan receptor-but, more likely, it is a protein.…”

CD10 expression by fusiform stromal cells in nasopharyngeal carcinoma correlates with tumor progression

“…Indeed, certain cytokines such as interleukin-1α, tumor necrosis factor, interleukin-6, and granulocyte macrophage colony stimulating factor increase lung fibroblasts CD10 expression during the inflammatory process [21]. On the other hand, transforming growth factor-β1 could decrease CD10 activity by reducing gene transcription or mRNA stability [4]. Furthermore, CD10 activity may be regulated by prostaglandin synthesis and cAMP [21].…”