Age dependent phenotype in KLF10 -/- mice

초록

Background: Aging is a natural and complex process, and a complete understanding of the molecular mechanisms to control it is not likely to be achieved shortly. Aging is closely connected with many common diseases such as heart disease, respiratory diseases, and cancer. KLF10 knockout mice provided an important understanding of the effects of signaling pathways on certain diseases. Despite several studies on the role of KLF10, aging remains to be revealed. Methods: To demonstrate if complete loss of KLF10 subsequently resulted in age-dependent phenotype we chose 4 different time points 0.5year, 1 year 1.5year and 2-year group. Body weight and clinical signs were checked every week. Results: Here, we found that KLF10 Knockout (KLF10-/-) mice progressively develop a syndrome resembling human aging, including hair loss, graying, and kyphosis, become apparent after 1 year. KLF10-/- mice develop a pathological condition that has the classical signs of autoimmune disease splenomegaly, lymphadenopathy, multiorgan inflammation with tissue damage, and elevated levels of proinflammatory cytokines. we observed an increased and abnormal Megakaryocytes s in the bone marrow and spleen with increased age compared to KLF10+/+mice. In the absence of KLF10 Th17 differentiation was also increased in KLF-10-deficient. MKs was increases and inducing Th17 twisting in response to foreign and self-antigens which can break immune tolerance in KLF10-/- mice, that effect was seen on multiple organ inflammation such as liver lungs kidney and heart. In addition, percentages of IFN- ? and IL-17A-producing cells were increased in KLF-10-deficient mice. Conclusion: KLF10?deficient mice develop spontaneous autoimmune disease with increasing aged. Collectively, these findings strongly suggest that KLF10 is required for proper dissolution of the immune response, and KLF10 removal is seriously harmful to the organism. These findings suggest that there may be a link between the abnormally presenc