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Effect of hypothalamic-hypophysary inhibitory factor on mesangial cell activation
A Rodríguez-Barbero1, C Martínez-Salgado, A M Rodríguez-López
1Instituto Reina Sofía de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
Insights
A novel hypothalamic-hypophysary inhibitory factor (HHIF) triggers mesangial cell contraction and proliferation. These cellular responses are linked to increased intracellular calcium levels, suggesting a new pathway for regulating kidney cell function.
Area of Science:
- Nephrology
- Cell Biology
- Endocrinology
Background:
- Mesangial cells play a crucial role in kidney function.
- Understanding factors that regulate mesangial cell activity is vital for kidney health.
- Sodium pump inhibitors can influence cellular processes.
Purpose of the Study:
- To investigate the effects of a specific sodium pump inhibitor, hypothalamic-hypophysary inhibitory factor (HHIF), on rat mesangial cells.
- To determine HHIF's impact on cell contraction, proliferation, and calcium mobilization.
- To elucidate the signaling pathways involved in HHIF-induced mesangial cell responses.
Main Methods:
- Primary cultures of rat mesangial cells were used.
- Effects of HHIF on rubidium uptake, cell surface area, DNA synthesis, and cell proliferation were measured.
- Changes in cytosolic free calcium and immediate early gene expression (c-fos, c-jun) were assessed.
- The role of verapamil and TMB-8 in modulating HHIF effects was examined.
Main Results:
- HHIF inhibited rubidium uptake in a dose-dependent manner.
- HHIF induced mesangial cell contraction and decreased planar cell surface area.
- HHIF significantly increased DNA synthesis and cell proliferation.
- HHIF elevated cytosolic free calcium levels and induced c-fos and c-jun mRNA expression.
- Verapamil and TMB-8 inhibited HHIF-induced contraction, proliferation, and calcium increase.
Conclusions:
- Hypothalamic-hypophysary inhibitory factor (HHIF) stimulates mesangial cell contraction and proliferation.
- These effects are mediated by an increase in cytosolic free calcium.
- HHIF represents a potential regulator of kidney mesangial cell function.
Abstract:
We examined the effect of a sodium pump inhibitor isolated from bovine hypothalamus and pituitary tissues on contraction, proliferation, and calcium mobilization in primary cultures of rat mesangial cells. Hypothalamic-hypophysary inhibitory factor (HHIF) inhibited rubidium uptake in a concentration-dependent manner (0.2 U/mL: 56.8 +/- 6.3% inhibition). It also induced a concentration- and time-dependent decrease in planar cell surface area. Maximal contraction (25 +/- 5% reduction in cell size) was reached at 60 minutes with a concentration of 0.2 U/mL. This effect was inhibited by both verapamil and TMB-8 (10(-5) mol/L). HHIF was also observed to increase DNA synthesis (0.2 U/mL: 4361 +/- 168 versus 2129 +/- 162 cpm per well under control conditions) and cell proliferation (0.2 U/mL: 52,290 +/- 1931 versus 10,512 +/- 121 cells per well under control conditions). Both effects were also inhibited by verapamil and TMB-8. Moreover, HHIF induced the expression of immediate early genes c-fos and c-jun mRNA. HHIF-induced effects were accompanied by an increase in cytosolic free calcium (203 +/- 58 versus 101 +/- 2 nmol/L under control conditions), which was inhibited by verapamil and TMB-8. In summary, HHIF induces mesangial cell contraction and proliferation; these effects seem to be mediated by an increase in cytosolic free calcium levels.