Browsing by Subject "RAGE"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    Hypertension accelerates age-related intrarenal small artery (IRSA) remodelling and stiffness in rats with possible involvement of AGEs and RAGE.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Ba, Yajing; Shi, Xiaoyun; Ke, Yilang; Lin, Xiaohong; Hong, Huashan
    Objectives. To study changes in morphology, advanced glycation end products (AGEs) and the AGEs receptor, RAGE, that occur with ageing in intrarenal small arteries (IRSAs) of spontaneously hypertensive rats (SHRs) and to investigate the possible roles of hypertension, AGEs and RAGE in the progression of IRSA remodelling and stiffness with ageing in rats. METHODS: Ageing SHRs and ageing normotensive Wistar Kyoto (WKY) rats were studied. The minimal renal vascular resistance (minRVR) was measured. Renal arcuate arteries (RAAs) and interlobular arteries (RILAs), the expression of α-smooth muscle actin, proliferating cell nuclear antigen, AGEs, RAGE and the plasma concentrations of AGEs were also examined. RESULTS: The IRSA minRVR, wall thickening, cell proliferation and collagen deposition in RILAs and RAAs gradually increased with age in SHRs and were much higher in 24-week-old SHRs than in age-matched WKY rats (p<0.05); these indexes in WKY rats were only elevated in the 72-week group (p<0.05). The expression of RAGE in the RAA and RILA tunica media in SHRs was upregulated by 24 weeks and 12 weeks (p<0.05), respectively, while AGEs levels in the plasma and in the IRSA tunica media were increased by 48 weeks (p<0.05) and increased gradually with age. The levels of both RAGE and AGEs in WKY rats were increased only at 72 weeks (p<0.05). CONCLUSION: Hypertension accelerates the development of age-related IRSA remodelling and stiffness in rats, which may be related to upregulation of RAGE in the IRSA tunica media and increased expression of AGEs at the late stage.
  • Thumbnail Image
    Publication
    Open Access
    Inflammatory risk factors and pathologies promoting Alzheimer’s disease progression: is RAGE the key?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Matrone, Carmela; Djellou, Mehdi; Taglialatela, Giulio; Perrone, Lorena
    Epidemiological studies reveal growing evidence that most cases of Alzheimer’s Disease (AD) likely involve a combination of genetic and environmental risk factors. Identifying and validating these risk factors remains one of the most critical scientific challenges. Several diseases appear to have strong implications for neurodegeneration leading to dementia. This risk encompasses different forms of cardiovascular disease, carotid atherosclerosis, history of hypertension or high cholesterol, Type II diabetes, stroke or transient ischemic attack and brain trauma. However, the molecular pathways that are common and central in the progression of these diseases and AD are not yet elucidated. Unveiling these critical mechanisms at the molecular level is necessary for the development of therapeutic strategies aimed at preventing AD progression. The Receptor for Advanced Glycation Endproducts (RAGE) plays a key role in all the diseases that represent a risk for AD. RAGE-mediated signaling also contributes to neurodegeneration in AD, suggesting that it may mediate the effect of risk factors in promoting AD. We will summarize the current knowledge on the role of RAGE in pathologies promoting AD and in AD progression. We will also provide evidence showing the relevance of RAGEinduced inflammation as a risk pathway that is implicated in AD pathophysiology.
  • Thumbnail Image
    Publication
    Open Access
    The receptor for advanced glycation end products is dispensable in a mouse model of oral and esophageal carcinogenesis
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Mark, Regina; Lorenzo Bermejo, Justo; Bierhaus, Angelika; Plinker, Peter K; Angel, Peter; Hess, Jochen
    Aberrant expression of the receptor for advanced glycation end products (RAGE) and its ligands, such as S100/Calgranulins, has been demonstrated in squamous cell carcinomas of the upper aerodigestive tract. However, the question whether RAGE signaling is causally linked with neoplastic transformation of keratinocytes in mucosal epithelia has not been addressed so far. We used the well-established mouse model of 4-nitroquinoline-1-oxide (4-NQO) induced tumorigenesis to investigate tumor development in control and RAGE-deficient (Rage-/- ) animals. Although 4-NQO induced lesions of the tongue and the esophagus showed strong induction of the RAGE ligands S100a8 and S100a9, we did not observe any significant difference in tumor incidence or multiplicity between control and Rage-/- mice. Furthermore, detailed analysis of tumor sections by histological and immunohistochemical staining revealed no difference in either the size or histological architecture of dysplastic lesions, tumor cell proliferation, or the number of inflammatory immune cells in the tumor microenvironment. Finally, we detected induced transcript and protein levels of the Toll-like receptor 4 (Tlr4) in 4-NQO induced lesions, suggesting that signaling via the S100- Tlr4 axis may compensate for the lack of RAGE in early stages of tumor development.