Yu Xin1, Xiangsheng Wang2, Ming Zhu3, Miao Qu4, Melia Bogari3, Li Lin3, Zin Mar Aung3, Wei Chen3, Xiaojun Chen3, Gang Chai5, Yan Zhang6. 1. Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, China; Shanghai Tissue Engineering Key Laboratory, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. 2. Shanghai Tissue Engineering Key Laboratory, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. 3. Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, China. 4. Clinic for Plastic, Hand and Burns Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany. 5. Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, China; Shanghai Tissue Engineering Key Laboratory, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: 13918218178@163.com. 6. Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, China; Shanghai Tissue Engineering Key Laboratory, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: 13651817522@163.com.
Abstract
BACKGROUND: Keloid is a skin fibrosis disease that characterised by invasive growth of fibroblasts and aberrant deposition of extracellular matrix. Studies indicated that keloid fibroblasts (KFs) is a class of 'activated' fibroblasts, which show accelerated proliferation and excessive extracellular matrix formation as compared with normal fibroblasts (NFs). However, the mechanism underlying keloid fibroblasts dysfunction is still unknown. OBJECTIVE: To verify CD26 expression difference between KFs and NFs, and investigate the function of CD26 positive fibroblasts in keloid progression. METHODS: KFs and NFs were isolated from Keloid tissues and normal skin tissues respectively. Flow cytometry was performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of different fibroblasts were analyzed by CCK8 assay and Ki 67 straining. Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and immunofluorescence. Scratching experiment and transwell assay were used to assess invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26 inhibitor to further investigated the function of CD26 fibroblasts in keloid disease. RESULT: CD26 expression was increased in KFs, and the proportion of CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the expression of profibrotic genes were increased in CD26+ fibroblasts, including TGF-β1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile, CD26+ fibroblasts showed stronger invasion ability as compared to CD26- fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues. CONCLUSION: Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression.
BACKGROUND: Keloid is a skin fibrosis disease that characterised by invasive growth of fibroblasts and aberrant deposition of extracellular matrix. Studies indicated that keloid fibroblasts (KFs) is a class of 'activated' fibroblasts, which show accelerated proliferation and excessive extracellular matrix formation as compared with normal fibroblasts (NFs). However, the mechanism underlying keloid fibroblasts dysfunction is still unknown. OBJECTIVE: To verify CD26 expression difference between KFs and NFs, and investigate the function of CD26 positive fibroblasts in keloid progression. METHODS: KFs and NFs were isolated from Keloid tissues and normal skin tissues respectively. Flow cytometry was performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of different fibroblasts were analyzed by CCK8 assay and Ki 67 straining. Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and immunofluorescence. Scratching experiment and transwell assay were used to assess invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26 inhibitor to further investigated the function of CD26 fibroblasts in keloid disease. RESULT: CD26 expression was increased in KFs, and the proportion of CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the expression of profibrotic genes were increased in CD26+ fibroblasts, including TGF-β1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile, CD26+ fibroblasts showed stronger invasion ability as compared to CD26- fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues. CONCLUSION: Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression.
Authors: Brett A Shook; Renee R Wasko; Guillermo C Rivera-Gonzalez; Emilio Salazar-Gatzimas; Francesc López-Giráldez; Biraja C Dash; Andrés R Muñoz-Rojas; Krystal D Aultman; Rachel K Zwick; Vivian Lei; Jack L Arbiser; Kathryn Miller-Jensen; Damon A Clark; Henry C Hsia; Valerie Horsley Journal: Science Date: 2018-11-23 Impact factor: 47.728
Authors: Fu Jun Li; Ranu Surolia; Huashi Li; Zheng Wang; Gang Liu; Tejaswini Kulkarni; Adriana V F Massicano; James A Mobley; Santanu Mondal; Joao A de Andrade; Scott A Coonrod; Paul R Thompson; Keith Wille; Suzanne E Lapi; Mohammad Athar; Victor J Thannickal; A Brent Carter; Veena B Antony Journal: Sci Transl Med Date: 2021-03-17 Impact factor: 17.956