New study reveals mechanisms for UVA1 phototherapy in scleroderma
Treatment uses ultraviolet light to ease lesions, reduce scarring
A new study shows that UVA1 phototherapy — a treatment strategy that uses specific wavelengths of ultraviolet light — may work to reduce scarring in scleroderma by activating the aryl hydrocarbon receptor (AhR).
This finding implies that activating the AhR protein may offer therapeutic benefits in the chronic autoimmune disease, according to researchers.
The study, “UVA1 irradiation attenuates collagen production via Ficz/AhR/MAPK signaling activation in scleroderma,” was published in the journal International Immunopharmacology.
Investigating how the treatment works
Scleroderma is characterized by fibrosis, or the excessive production of scar tissue. UVA1 phototherapy has been shown to ease scleroderma lesions and reduce the production of collagen, the protein that forms the main component of scar tissue in the body.
However, the molecular mechanisms by which UVA1 phototherapy works remain incompletely understood. Now, a team of scientists in China sought to learn more by investigating the treatment’s effects on the underlying disease mechanisms.
Specifically, they tested the hypothesis that UVA1 phototherapy might reduce collagen production by increasing levels of a molecule called 6-formylindolo[3,2-b]carbazole — Ficz for short.
Tryptophan is an amino acid, one of the building blocks used to make proteins in the body. When tryptophan is hit by ultraviolet light, it can trigger a chemical change to produce Ficz.
Ficz can bind to the protein receptor AhR, and prior research has suggested that activating AhR can reduce the production of collagen.
“We wonder whether UVA1 phototherapy could stimulate Ficz production to participate in the anti-fibrosis process [in] scleroderma,” the researchers wrote.
The scientists conducted studies using fibroblasts, the main cells responsible for making collagen, that were collected from the skin of 12 people with scleroderma. Among them, six had systemic scleroderma and six localized disease.
Results showed that patient fibroblasts did not have detectable Ficz prior to phototherapy, but levels of this molecule rose markedly within 30 minutes of exposure to UVA1 phototherapy. Following the rise in Ficz, there were changes in the cellular location of AhR consistent with the protein receptor becoming activated.
“These results indicated that UVA irradiation of [scleroderma] fibroblasts could induce Ficz production and activate AhR,” the researchers wrote.
The increase in Ficz levels was accompanied by a decrease in collagen production, as well as an increase in matrix metalloproteinase-1 (MMP1), a protein that can break down collagen.
The researchers then engineered the cells so they could not produce AhR protein. In these cells, the effect of UVA1 phototherapy — in terms of reducing collagen and boosting MMP-1 — was markedly diminished.
This suggests that the “effect of [UVA1] phototherapy is effected at least partly through activation of the AhR pathway,” the researchers wrote.
When AhR is activated, it sets off a chain of molecular events that activates the proteins ERK and MAPK, which trigger further downstream effects in the cell. Blocking the activity of these proteins also diminished the anti-fibrotic effect of UVA1 phototherapy in scleroderma patient cells, data showed.
Collectively, the data are consistent with the model that UVA1 phototherapy reduces fibrosis at least in part by triggering the production of Ficz and thereby activating AhR. The researchers noted that this was a small study and more research is needed to confirm the findings.
About the Author
