Hepatocyte growth factor regulates angiotensin converting enzyme expression.

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Hepatocyte growth factor (HGF) is known for tissue healing and anti-fibrotic properties, but its precise mechanisms remain unclear.
• Somatic angiotensin-converting enzyme (ACE) has been implicated in fibrotic processes.
• Understanding HGF's effect on ACE expression is crucial for elucidating its role in fibrosis.

Purpose of the Study:

• To investigate the effects of HGF on ACE expression in bovine pulmonary artery endothelial cells (BPAEC).
• To elucidate the molecular mechanisms by which HGF influences ACE gene transcription.
• To compare the regulatory effects of HGF with phorbol ester (PMA) on ACE expression.

Main Methods:

• Treatment of BPAEC with HGF and PMA.
• Measurement of ACE mRNA levels using reverse transcription-PCR.
• Assay of ACE activity using protease assays.
• Luciferase reporter assays to assess promoter activity.
• Electrophoretic mobility shift assays (EMSA) to analyze transcription factor binding.
• Site-directed mutagenesis of the ACE promoter.

Main Results:

• Short-term HGF treatment transiently increased ACE mRNA and activity, while long-term treatment suppressed them.
• PMA induced a sustained increase in ACE mRNA and activity.
• Both HGF and PMA activated the ACE promoter via the Egr-1 binding site.
• HGF-induced transcription was primarily mediated by Egr-1 activation.
• PMA-induced transcription involved Egr-1 and additional transcription factors.

Conclusions:

• HGF transiently upregulates ACE gene transcription through Egr-1 activation in endothelial cells.
• The regulatory mechanism of ACE by HGF differs from that of PMA, which involves Egr-1 and other factors.
• These findings contribute to understanding the complex roles of HGF and ACE in cellular processes and potentially in fibrotic diseases.