Background:

Using metabolomic approach, we previously reported that lung tryptophan levels were significantly increased in IPF. However, the role of tryptophan in IPF pathogenesis remains unclear. we investigated whether regulation of tryptophan modulate severity of lung fibrosis and to find its possible mechanism.

Aims:

We investigated whether regulation of tryptophan modulate severity of lung fibrosis and to find its possible mechanism.

Methods:

We measured expression of main extracellular matrix components in MRC-5 cells with or without tryptophan. IPF primary fibroblasts were used to perform proliferation assay and measurement of tryptophan hydroxylase (TPH-1). Exogenous tryptophan was administrated in the bleomycin (BLM) exposed mice.

Results:

In IPF lung lysates and fibroblast, TPH-1 protein levels were significantly increased than controls. Treatment of tryptophan increased collagen, fibronectin and a-SMA expressions in MRC5 cells. Tryptophan dramatically augments fibroblast proliferation. Treatment of tryptophan activate AKT-mTOR C1 pathway molecules in IPF fibroblast. Exogenous tryptophan promotes BLM-induced lung damage and fibrosis in mice.

Conclusions:

These findings suggest that overproduction of tryptophan may contribute to the IPF pathogenesis and regulation of tryptophan pathway may have therapeutic potential in preventing lung fibrosis.

This study was supported by Korea Environmental Industry & Technology Institute (2021003310007, 2022003310009)