Differential control of murine aldose reductase and fibroblast growth factor (FGF)-regulated-1 gene expression in NIH 3T3 cells by FGF-1 treatment and hyperosmotic stress

Abstract

Aldose reductase (AR) is an NADPH-dependent aldo-keto reductase implicated in cellular osmoregulation and detoxification. Two distinct murine genes have been identified that are predicted to encode proteins with significant amino acid sequence identity with mouse AR: mouse vas deferens protein and fibroblast growth factor (FGF)-regulated-1 protein (FR-1). Here we report that the AR and FR-1 genes are differentially regulated in NIH 3T3 fibroblasts. FGF-1 stimulation of quiescent cells induces both AR and FR-1 mRNA levels, but the effect on FR-1 mRNA expression is significantly greater. FGF-1 treatment also increases FR-1 protein expression, as determined by Western-blot analysis using FR-1-specific polyclonal antiserum. Calf serum stimulation of quiescent cells increases AR mRNA expression but not FR-1 mRNA expression. Finally, when NIH 3T3 cells are grown in hypertonic medium, AR mRNA levels are significantly increased whereas FR-1 mRNA levels are only slightly up-regulated. These results indicate that the AR and FR-1 genes are differentially regulated in murine fibroblasts by two different growth-promoting agents and by hyperosmotic stress. Therefore these structurally related enzymes may have at least some distinct cellular functions; for example, although both AR and FR-1 activity may be important for the metabolic changes associated with cellular proliferation, AR may be the primary aldo-keto reductase involved in cellular osmoregulation.

Involvement of Aldose Reductase in Vascular Smooth Muscle Cell Growth and Lesion Formation After Arterial Injury

“…Stimulation of NIH 3T3 cells with FGF or serum 26 and of astrocytes with FGF or endothelial growth factor 27 increases the steady-state abundance of AR mRNA. Moreover, AR is the most prominent tumor-associated antigen in chemically induced rat hepatomas and transformed rat liver cell lines, 22 and its expression in hepatomas is also stimulated by FGF.…”

Aldose Reductase Regulates Growth Factor-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Colon Cancer Cells

“…Further, we (17) and others (39)(40)(41) have shown earlier that growth factors and cytokines transcriptionally activate AR, which would facilitate growth factors and cytokine signals that induce COX-2. These observations suggest that AR is a growth-responsive protein, which may be involved in facilitating metabolic changes that accompany growth of colon cancer cells.…”

Aldose Reductase Mediates Mitogenic Signaling in Vascular Smooth Muscle Cells

“…Stimulation of NIH 3T3 cells by FGF-1 (and to a lesser extent by FGF-2, epidermal growth factor, and phorbol esters) leads to a dramatic increase in the expression of an aldo-keto reductase, FR-1 (21), which is related to AR in structure and function (21,22). The AR protein itself is also increased by growth factors in the 3T3 fibroblasts (23), astrocytes (24), and vascular smooth muscle cells (VSMC) (10). Although the quiescent VSMC of the tunica media do not express detectable levels of AR, the expression of the enzyme is markedly induced during vascular inflammation or growth (10,11).…”