NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury

Area of Science:

• Nephrology
• Molecular Biology
• Cell Biology

Background:

• Glomerular fibrin deposition suggests increased coagulation in kidney disease.
• Tissue factor (TF) is a key coagulation factor with diverse biological roles.
• TF is upregulated by hypoxia in cancer cells, and hypoxic podocyte injury is a recent hypothesis.

Purpose of the Study:

• To investigate the expression of tissue factor (TF) in human podocytes under hypoxic conditions.
• To elucidate the role of TF in hypoxia-induced podocyte injury.

Main Methods:

• Human podocytes were subjected to hypoxic or normoxic conditions.
• Quantitative RT-PCR and ELISA were used to analyze TF and TFPI mRNA and protein levels.
• Small interfering RNA (siRNA) was used to knockdown TF, Egr-1, and HIF-1α; NF-κB activity was assessed using PDTC.

Main Results:

• Hypoxia significantly increased TF mRNA and protein levels while decreasing TFPI.
• TF expression was NF-κB dependent and not affected by Egr-1 knockdown.
• Hypoxia-induced podocyte injury, including CD2AP downregulation and actin reorganization, was attenuated by TF knockdown.

Conclusions:

• Hypoxia upregulates TF expression in human podocytes through an NF-κB-dependent pathway.
• TF plays a critical role in mediating hypoxic podocyte injury.