Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that α2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.
30 November 2018 in Intractable & Rare Diseases Research
A 94-year-old woman was admitted to our hospital with a 5-day history of painful redness in the left lower leg. She was diagnosed with cellulitis and initiated antibiotic therapy with cefazolin. After two days, she presented with an extremely high fever (39.9°C), high C-reactive protein level (256 mg/L; normal, < 3), and signs of disseminated intravascular coagulation. In bacteriological examination, Streptococcus pseudoporcinus was detected from her lower leg wound purulence. An antibiogram revealed multidrug resistance except for cefepime, carbapenems, and vancomycin. We changed the antibiotics to cefepime and vancomycin according to the antibiogram and administered immunoglobulin concurrently. As the result of these therapies, her conditions gradually resolved over two weeks. S. pseudoporcinus, one of the β-hemolytic Streptococcus species recently described, has been isolated from the genitourinary tract of women. To our knowledge, this is the first case of cellulitis caused by S. pseudoporcinus. Typically, most antibiotics indicate adequate drug susceptibilities of S. pseudoporcinus, but in our case, multidrug resistance contributed to the prolonged duration of treatment. Because the colonization of S. pseudoporcinus in healthy individuals is not rare, it could become an important pathogen in elderly people and in those who have underlying medical conditions, as with other β-hemolytic Streptococci.
3 March 2020 in Journal of Investigative Dermatology