Keloid is an abnormal fibrotic disease after cutaneous injury characterized by exaggerated
scar tissue formation, which often extends beyond the boundaries of the original
wound. Although chronic
inflammation is known to be associated with the excessive
inflammation in
keloid tissue, there are few studies on the role of autophagy in the pathogenesis of
keloid. In this study, we evaluated the pattern of autophagy in
keloid fibroblasts (KF) and normal fibroblasts (NF). Expression of HIF-1α, STAT3 and autophagic flux markers were evaluated in KF and NF. Defective autophagy caused by
IL-17 was evaluated, and the relationship between defective autophagy and necroptosis was also examined. The expression of
IL-17, HIF-1α and STAT3 was significantly increased in
keloid tissue, and autophagosome-to autophagolysosome conversion was defective in KF.
IL-17 treatment significantly elevated the expression of STAT3 and HIF-1α in NF and caused defective autophagy, which was reversed by HIF-1α inhibitor. In addition, the defective autophagy was associated with the increased necroptosis and
fibrosis. In
keloid tissue, the elevated necroptosis marker was confirmed, and with the HIF-1α inhibitor, the defective autophagy, necroptosis and
fibrosis was decreased in KF. In conclusion, autophagy was defective in
keloid tissue, which was associated with increased necroptosis and
fibrosis. The IL-17-STAT3-HIF-1α axis was involved in defective autophagy in KF, and this suggests that targeting the axis could alleviate chronic
inflammation in
keloid disease.