MMP-1 and ADAM10 as Targets for Therapeutic Intervention in Idiopathic Pulmonary Fibrosis.
Zhihong PengMohini Mohan KonaiLuis F Avila-CobianMan WangShahriar MobasheryMayland ChangPublished in: ACS pharmacology & translational science (2022)
Idiopathic pulmonary fibrosis (IPF), a fatal disease characterized by excessive matrix degradation and fibrosis, destroys the lung architecture and results in the inability of the lungs to absorb oxygen. The cause(s) of IPF is unknown and current treatments are palliative. Matrix metalloproteinases (MMPs) and A Disintegrin And Metalloproteinases (ADAMs) likely play roles in IPF progression. However, specific MMPs and ADAMs in IPF have not been identified due to challenges in MMP/ADAM profiling. We employed a designer affinity resin that binds exclusively to the active forms of MMPs and ADAMs and found by mass spectrometry higher levels of active MMP-1, ADAM9, ADAM10, and ADAM17 in lung tissues of IPF patients. Inhibition of MMP-1 and ADAM10 with the small-molecule inhibitor GI254023X in an in vitro lung fibrosis assay decreased the profibrotic protein α-smooth muscle actin (α-SMA). Our results indicate that inhibition of MMP-1 and ADAM10 may hold promise in treatment of IPF.
Keyphrases
- idiopathic pulmonary fibrosis
- interstitial lung disease
- cell migration
- small molecule
- smooth muscle
- mass spectrometry
- end stage renal disease
- randomized controlled trial
- chronic kidney disease
- gene expression
- ejection fraction
- single cell
- protein protein
- body mass index
- high throughput
- systemic sclerosis
- ms ms
- binding protein
- liver fibrosis
- weight gain
- gas chromatography
- amino acid