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.

Since April 2015, post-mastectomy breast reconstruction has been covered by the Korean National Health Insurance Service (NHIS). The frequency of these procedures has increased very rapidly. We analyzed data obtained from the Big Data Hub of the Health Insurance Review and Assessment Service (HIRA) and determined annual changes in the number of breast reconstruction procedures and related trends in Korea. We evaluated the numbers of mastectomy and breast reconstruction procedures performed between April 2015 and December 2018 using data from the HIRA Big Data Hub. We determined annual changes in the numbers of total, autologous, and implant breast reconstructions after NHIS coverage commenced. Data were analyzed using Microsoft Excel. The post-mastectomy breast reconstruction rate increased from 19.4% in 2015 to 53.4% in 2018. In 2015, implant reconstruction was performed in 1,366 cases and autologous reconstruction in 905 (60.1% and 39.8%, respectively); these figures increased to 3,703 and 1,570 (70.2% and 29.7%, respectively) in 2018. Free tissue transfer and deep inferior epigastric perforator flap creation were the most common autologous reconstruction procedures. For implant-based reconstructions, the rates of directto-implant and tissue-expander breast reconstructions (first stage) were similar in 2018. This study summarizes breast reconstruction trends in Korea after NHIS coverage was expanded in 2015. A significant increase over time in the post-mastectomy breast reconstruction rate was evident, with a trend toward implant-based reconstruction. Analysis of data from the HIRA Big Data Hub can be used to predict breast reconstruction trends and convey precise information to patients and physicians.

: The pathogenesis of keloids has not been elucidated, and the disease is thought to be caused by abnormal secretion of proinflammatory mediators and irregular responses to other inflammatory signals mediated by keloid fibroblasts (KFs). In this study, we investigated whether a local increase in interleukin IL-17 in keloid tissues stimulates the production of stromal cell–derived factor-1 (SDF-1) in KFs causing further recruitment of IL-17-producing T helper 17 (Th17) cells, which subsequently creates a positive feedback loop. Histological assessment was performed and the change in the expression of IL-17, IL-1β, IL-6, and TNF-α which of fibrosis and inflammation associated markers was examined. In addition, fibroblasts were treated with IL-17 in the presence or absence of STAT3 inhibitor STA-21; SDF-1 levels and fibrosis genes were measured. Our results showed that fibrotic reaction and expression of proinflammatory cytokines including IL-17 were most prominent in the growing margin (perilesional area) of keloid tissue and Th17 cells significantly infiltrated the perilesional area. In addition, IL-17 upregulated the expression of SDF-1, collagen, and α-SMA in KFs. Finally, STA-21 decreased SDF-1α expression and the expression of fibrosis genes in KFs even after IL-17 stimulation. Our study demonstrated that a local increase in IL-17 in keloid tissues stimulates the production of SDF-1 in KFs causing further recruitment of IL-17-producing T helper 17 (Th17) cells, which subsequently creates a positive feedback loop. These findings suggest that STAT3 inhibition can be used to treat keloid scars by reversing the vicious cycle between Th17 cells and KFs.

Kim SM, et al. J Korean Med Sci. 2014 Nov;29(Suppl 3):S249-S253. http://dx.doi.org/10.3346/jkms.2014.29.S3.S249

Lee JH, et al. J Korean Med Sci. 2014 Nov;29(Suppl 3):S217-S221. http://dx.doi.org/10.3346/jkms.2014.29.S3.S217