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UVA irradiation leads to photoaging including clinical features such as wrinkle formation, reduced recoil capacity and blister formation of the skin. Besides synthesis of the extracellular matrix, its regulated degradation by various matrix-metalloproteinases (MMPs) determines the amount and the composition of the extracellular matrix within the dermis and(More)
Uncontrolled macrophage activation is now considered to be a critical event in the pathogenesis of chronic inflammatory diseases such as atherosclerosis, multiple sclerosis, and chronic venous leg ulcers. However, it is still unclear which environmental cues induce persistent activation of macrophages in vivo and how macrophage-derived effector molecules(More)
We studied the mechanisms underlying the severely impaired wound healing associated with human leukocyte-adhesion deficiency syndrome-1 (LAD1) using a murine disease model. In CD18(-/-) mice, healing of full-thickness wounds was severely delayed during granulation-tissue contraction, a phase where myofibroblasts play a major role. Interestingly, expression(More)
The skin is increasingly exposed to ambient UV-irradiation thus increasing risks for photooxidative damage with long-term detrimental effects like photoaging, characterized by wrinkles, loss of skin tone and resilience. Photoaged skin displays alterations in the cellular component and extracellular matrix with accumulation of disorganized elastin and its(More)
Singlet oxygen has been postulated to be generated by Ultraviolet (UV) A irradiation of mammalian cells. We studied the role of singlet oxygen in the downstream signaling of the complex UV response leading to the induction of matrix-metalloproteinase-1 (interstitial collagenase/MMP-1). Exposure of cultured human fibroblasts to singlet oxygen, generated in a(More)
The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the(More)
Monoubiquitination of core histone 2A (H2A-K119u) has a critical role in gene regulation in hematopoietic differentiation and other developmental processes. To explore the interplay of histone H2A deubiquitinase Myb-like SWIRM and MPN domain containing1 (2A-DUB/Mysm1) with the p53 axis in the sequential differentiation of mature lymphocytes from(More)
Singlet oxygen generated in a dark reaction by thermodissociation of an endoperoxide (NDPO2) elicits an increase in mRNA of interstitial collagenase (MMP-1) in cultured human fibroblasts. The effect is enhanced in deuterium oxide-based medium and is abolished in the presence of non-toxic doses of sodium azide. In contrast, the mRNA level of the tissue(More)
The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by UV-induced reactive oxygen species (ROS). Increased ROS load has been implicated in several pathological states including photoaging and photocarcinogenesis of the skin. Large(More)
The cell-cycle regulating gene, p16INK4A, encoding an inhibitor of cyclin-dependent kinases 4 and 6, is considered to play an important role in cellular aging and in premature senescence. Although there is an age-dependent increase of p16INK4A expression in human fibroblast senescence in vitro, no data are available regarding the age dependency of p16INK4A(More)