Hyaluronic Acid is Overexpressed in Fibrotic Lung Tissue and Promotes Collagen Expression

In 30 to 70% of systemic sclerosis patients, the disease progresses to the lungs and internal organs. This lung fibrosis (i.e. the overexpression of collagen) is the major cause of morbidity and mortality in scleroderma. The overexpression of collagen is accompanied by the overexpression of other extracellular matrix molecules including hyaluronic acid (HA). To evaluate the possibility that HA regulates collagen expression, we treated lung fibroblasts with HA oligomers (fragments of HA that block HA binding to its cell surface receptors CD44, TLR2, and TLR4). Both HA oligomers and lipopolysaccharide (LPS, another TLR2 and TLR4 ligand) had major effects on collagen expression. In addition, HA oligomers affected the expression of the collagen-degrading enzyme MMP-2. These observations open up the possibility that reagents that affect signaling cascades initiated by HA or LPS will have therapeutic value in inhibiting the progression of lung fibrosis in human patients.