Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped...Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.展开更多
Carcinoma-associated fibroblasts(CAFs) function as a double-edged sword in tumor progression. However,factors affecting the transition between tumor promotion and inhibition remain to be investigated. Here, we found t...Carcinoma-associated fibroblasts(CAFs) function as a double-edged sword in tumor progression. However,factors affecting the transition between tumor promotion and inhibition remain to be investigated. Here, we found that the transition was determined by stiffness heterogeneity of the tumor stroma in which tumor cells and CAFs were grown.When tumor cells were grown on a rigid plastic substrate,supernatants from CAFs inhibited the cytotoxic effects of 5-fluorouracil. In contrast, when tumor cells were grown on a soft substrate(5.3 kPa), supernatants from CAFs grown on a soft substrate increased the cytotoxicity of 5-fluorouracil. The diverse effects of CAFs were mediated by mechanotransduction factors, including stroma stiffness-induced cytokine expression in CAFs and signal transduction associated with stress fiber formation of CAFs. Moreover, we found that the cytokine expression in CAFs was regulated by nuclear Yesassociated protein, which changed according to cell stiffness,as characterized by atomic force microscopy. Overall, these findings suggested that modulating the mechanotransduction of the stroma together with CAFs might be important for increasing the efficacy of chemotherapy.展开更多
[Objectives] To investigate expression of MMP-1 in the scar tissue of skin and oral mucosa,and to explore if there is the significance of MMP-1 in the scar of skin and oral mucosa.[Methods]All samples were collected f...[Objectives] To investigate expression of MMP-1 in the scar tissue of skin and oral mucosa,and to explore if there is the significance of MMP-1 in the scar of skin and oral mucosa.[Methods]All samples were collected from surgical postoperative soft tissue from Department of Oral and Maxillofacial Surgery and Plastic Surgery in the Affiliated Qingdao Hiser Medical Center of Qingdao University Medical College,including 22 samples of dermal scar tissue,20 samples of normal skin tissue,and 13 samples of oral mucosal scar tissue,and 20 samples of normal oral mucosal tissue. HE staining was used to observe the morphology and collagen arrangement of fibroblasts in the scar tissue,the expression of MMP-1 in different tissue was observed by immunohistchemical staining. [Results] The positive expression rates of MMP-1 in skin scar tissue,oral mucousal scar tissue,normal skin tissue and normal mucosal tissue were 27. 27%,69. 23%,5. 00%,10. 00%. Comparison of positive expression of MMP-1 in skin scar tissue and oral mucosal scar tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that of MMP-1 in skin scar tissue,and the statistically significant difference was found between them( P < 0. 05).Comparison of positive expression of MMP-1 in skin scar tissue and normal skin tissue: the positive expression in skin scar tissue was higher than that in normal skin,and the statistically significant difference was found between them( P < 0. 05). Comparison of positive expression of MMP-1 in oral mucosal scar tissue and normal oral mucosal tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that in normal mucosal tissue,and the statistically significant difference was found between them( P < 0. 05). Comparison of positive expression of MMP-1 in normal oral mucosal tissue and normal skin tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that in normal mucosal tissue,and there was no statistically significant difference between them( P > 0. 05). [Conclusions] The positive expression of MMP-1 was different from that in the scar tissue of the oral mucosa,indicating that MMP-1 might be related to the severity of scar formation in different tissues.展开更多
Objective： To explore the influence of charred Gossamer urocteae （CGU） on the functions of primary cultured mouse oral fibroblasts and reveal its mechanism in wound healing. Methods： CGU was extracted with differe...Objective： To explore the influence of charred Gossamer urocteae （CGU） on the functions of primary cultured mouse oral fibroblasts and reveal its mechanism in wound healing. Methods： CGU was extracted with different solvents and ethanol extract （EE）, ethyl acetate fraction （EF）, n-butanol fraction （BF） and aqueous fraction （AF） were obtained. The effects of different fractions on the proliferation, matrix metaUoproteinase-2,9 （MMP-2,9） activities, synthesis of collagen and tissue inhibitor of metalloproteinase 1 （TIMP-1） in the mouse oral fibroblasts were determined by MTT, gelatin zymography, chloramine-T method, and enzyme-linked immunosorbent assay （ELISA） respectively. Results： EE, EF and BF at high concentrations could significantly inhibit proliferation of fibroblasts （P〈0.05 or P〈0.01）, and at low concentrations EF and BF could promote proliferation of fibroblasts, and BF and AF could significantly inhibit collagen synthesis （P〈0.05 or P〈0.01）. EE, EF and AF at high concentrations could significantly increase the MMP-9 activity, and BF and AF could significantly inhibit synthesis of TIMP-1. Conclusion： CGU at high concentrations can inhibit the proliferations of fibroblasts and synthesis of collagen, and in healing of wound, CGU at high concentrations possibly has the functions of anti-fibrosis and anti-scar, and the mechanism to promote degradation of collagen is possibly related to the increase in MMP-9 activity and the inhibition of TIMP-1 synthesis.展开更多
文摘Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.
基金financially supported by the Postdoctoral Science Foundation Program of Chinese Academy of Medical Sciences & Peking Union Medical Collegethe National Natural Science Foundation of China (NSFC) (31470905)National Institutes of Health/National Cancer Institute (NIH/NCI) Grant R21, CA208196
文摘Carcinoma-associated fibroblasts(CAFs) function as a double-edged sword in tumor progression. However,factors affecting the transition between tumor promotion and inhibition remain to be investigated. Here, we found that the transition was determined by stiffness heterogeneity of the tumor stroma in which tumor cells and CAFs were grown.When tumor cells were grown on a rigid plastic substrate,supernatants from CAFs inhibited the cytotoxic effects of 5-fluorouracil. In contrast, when tumor cells were grown on a soft substrate(5.3 kPa), supernatants from CAFs grown on a soft substrate increased the cytotoxicity of 5-fluorouracil. The diverse effects of CAFs were mediated by mechanotransduction factors, including stroma stiffness-induced cytokine expression in CAFs and signal transduction associated with stress fiber formation of CAFs. Moreover, we found that the cytokine expression in CAFs was regulated by nuclear Yesassociated protein, which changed according to cell stiffness,as characterized by atomic force microscopy. Overall, these findings suggested that modulating the mechanotransduction of the stroma together with CAFs might be important for increasing the efficacy of chemotherapy.
基金Supported by Supported by Technology Research and Development Program of Qingdao[11-2-3-4-(2)-nsh]Affiliated Qingdao Hiser Medical Center of Qingdao University Medical College
文摘[Objectives] To investigate expression of MMP-1 in the scar tissue of skin and oral mucosa,and to explore if there is the significance of MMP-1 in the scar of skin and oral mucosa.[Methods]All samples were collected from surgical postoperative soft tissue from Department of Oral and Maxillofacial Surgery and Plastic Surgery in the Affiliated Qingdao Hiser Medical Center of Qingdao University Medical College,including 22 samples of dermal scar tissue,20 samples of normal skin tissue,and 13 samples of oral mucosal scar tissue,and 20 samples of normal oral mucosal tissue. HE staining was used to observe the morphology and collagen arrangement of fibroblasts in the scar tissue,the expression of MMP-1 in different tissue was observed by immunohistchemical staining. [Results] The positive expression rates of MMP-1 in skin scar tissue,oral mucousal scar tissue,normal skin tissue and normal mucosal tissue were 27. 27%,69. 23%,5. 00%,10. 00%. Comparison of positive expression of MMP-1 in skin scar tissue and oral mucosal scar tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that of MMP-1 in skin scar tissue,and the statistically significant difference was found between them( P < 0. 05).Comparison of positive expression of MMP-1 in skin scar tissue and normal skin tissue: the positive expression in skin scar tissue was higher than that in normal skin,and the statistically significant difference was found between them( P < 0. 05). Comparison of positive expression of MMP-1 in oral mucosal scar tissue and normal oral mucosal tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that in normal mucosal tissue,and the statistically significant difference was found between them( P < 0. 05). Comparison of positive expression of MMP-1 in normal oral mucosal tissue and normal skin tissue: the positive expression rate of MMP-1 in oral mucosal scar tissue was higher than that in normal mucosal tissue,and there was no statistically significant difference between them( P > 0. 05). [Conclusions] The positive expression of MMP-1 was different from that in the scar tissue of the oral mucosa,indicating that MMP-1 might be related to the severity of scar formation in different tissues.
文摘Objective： To explore the influence of charred Gossamer urocteae （CGU） on the functions of primary cultured mouse oral fibroblasts and reveal its mechanism in wound healing. Methods： CGU was extracted with different solvents and ethanol extract （EE）, ethyl acetate fraction （EF）, n-butanol fraction （BF） and aqueous fraction （AF） were obtained. The effects of different fractions on the proliferation, matrix metaUoproteinase-2,9 （MMP-2,9） activities, synthesis of collagen and tissue inhibitor of metalloproteinase 1 （TIMP-1） in the mouse oral fibroblasts were determined by MTT, gelatin zymography, chloramine-T method, and enzyme-linked immunosorbent assay （ELISA） respectively. Results： EE, EF and BF at high concentrations could significantly inhibit proliferation of fibroblasts （P〈0.05 or P〈0.01）, and at low concentrations EF and BF could promote proliferation of fibroblasts, and BF and AF could significantly inhibit collagen synthesis （P〈0.05 or P〈0.01）. EE, EF and AF at high concentrations could significantly increase the MMP-9 activity, and BF and AF could significantly inhibit synthesis of TIMP-1. Conclusion： CGU at high concentrations can inhibit the proliferations of fibroblasts and synthesis of collagen, and in healing of wound, CGU at high concentrations possibly has the functions of anti-fibrosis and anti-scar, and the mechanism to promote degradation of collagen is possibly related to the increase in MMP-9 activity and the inhibition of TIMP-1 synthesis.
