H2020Индивидуална стипендия2018–2020

IRONAGE · Iron as a driver of fibrosis and regeneration

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2018-04-01 → 2020-05-26
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Биологичната връзка между стареенето и фиброзата се изследва чрез анализи на белезите по вътрешни органи, като сърцето или белите дробове. Разбирането на тези процеси е важно, тъй като фиброзните заболявания причиняват голям брой смъртни случаи в Европейския съюз.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Iron as a driver of fibrosis and regeneration

The European Commission projects that the ratio of the very elderly population (above 80 years) will more than double in the EU over the next fifty years. Healthcare and long-term care expenditures are expected to rise due to the increase in the prevalence of aging associated diseases. Among the top of the list in aging associated diseases are fibrotic diseases. Estimates are that fibrotic diseases cause one third of the death cases in the EU. Fibrotic diseases originate from scar formation in the internal organs. As the scar tissue progressively grows, it impedes the function of the organ, and leads to a decline in health. The incidence of fibrotic diseases increases with age exponentially. Fibrosis can affect many organs. Fibrotic scars can form in the heart leading to cardiac arrest, lung fibrosis leads to a decline in respiratory capacity, and fibrosis in the kidneys or in the liver lead to a general health decline. Fibrotic diseases to date have no cure, and this is because of the limited understanding of their pathobiology. The overall objective of this action was to investigate the biology that links fibrotic diseases to aging.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

I have worked over the last five years on understanding how ion channels control inflammation, immunity, metabolism and cancer, with a strong emphasis on Ca2+ signaling. Now, I would like to take advantage of my diverse background in cation signaling and inflammation and integrate it with the outstanding expertise of Manuel Serrano´s lab in regeneration and aging, to ask fundamental questions on the role of iron in regulation of plasticity and fibrosis. Clinical reports have described local deposition of iron around fibrotic tissues, although the significance of this remains poorly understood and unexplored. My unifying hypothesis is that fibrosis is the manifestations of ongoing free-iron release into injured organs and tissues, which without clearance maintains chronic inflammation and prevents regeneration. The project is divided as follows: Objective #1 – Iron induced inflammation: the impact of free-iron on inflammatory cytokine and chemokine expression and signaling pathways. I have preliminary data indicating that free-iron is a potent inducer of inflammatory cytokines in fibroblasts. Objective #2 – Free-iron as a causative of fibrosis: effect of iron on cellular senescence and on mouse models of fibrosis; and iron homeostasis in human patients with fibrosis. In vitro, I have found that free-iron is an inducer of senescence. Furthermore, in a pilot study, I have found that bleomycin-induced lung fibrosis in mice is accompanied by high levels of iron deposition. Objective #3: Iron clearance and regeneration: Effects of free-iron and iron induced cytokines on acquired plasticity in vitro and on wound healing. Surprisingly, my preliminary data indicate that chelation of free-iron completely blocks acquisition of pluripotency, but has no effect on expansion of stem cells. I anticipate that the completion of this action will yield new fundamental insights into the underlying mechanisms of fibrosis and regeneration, and will allow me the transit to independence.""

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) · BarcelonaКоординаторИспания