Telomeres and kidney fibrosis
Kidney fibrosis leads to kidney failure, a disease that requires lifelong dialysis. The incidence of fibrosis is increasing due to the aging of the population. The laboratory of Telomeres and Telomerase Group at the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncológicas, CNIO) is developing methods for the treatment of kidney fibrosis, affecting one of the causes of aging – telomere shortening.
Aging is the cause of many diseases. Previously, researchers have suggested that it is possible to treat them by influencing aging-related processes, in particular, the shortening of telomeres. They have already managed to cure pulmonary fibrosis and infarction in mice by lengthening telomeres. Now they have focused on kidney fibrosis, as all the data indicate that telomere shortening is at the heart of this disease.
Kidney fibrosis is accompanied by excessive scarring of the renal tissue, which is replaced by fibrous tissue and loses its functions. It is estimated that 11% of people over 65 years of age suffer from moderate chronic renal failure. According to the results of the study, short telomeres enhance the process of epithelial-to-mesenchymal transition (EMT) in the kidneys, which is important for the regeneration and normal functioning of the body, and also underlies the pathological scarring of tissues in fibrosis and cancer. Despite all the novelty, the discovery was not unexpected, since it was known that overexpression of genes involved in EMT can lead to renal fibrosis.On the other hand, it has already been described that patients with renal fibrosis have shorter telomeres. Therefore, the authors deliberately looked for changes in the expression of genes involved in EMT in mice with short telomeres and renal fibrosis.
A group of researchers created two mouse models of kidney fibrosis, either combining telomerase deficiency to induce telomere shortening and reduced folic acid (vitamin B9) intake to worsen kidney function, or blocking the expression of Trf1 protein, a component of the telomere protective complex, in the kidneys.
The first model demonstrated that telomere shortening alone is not enough to cause kidney fibrosis, and this is logical, because the disease does not affect 100% of elderly people. However, if mice with short telomeres were exposed to low doses of folic acid, they developed kidney fibrosis.
The second model helped determine whether telomeres really play a causal role in fibrosis. The absence of Trf1 protein, which is involved in the regulation of telomere functions, also led to the development of kidney fibrosis in mice.
As another demonstration of the role of telomeres in the development of kidney fibrosis, the authors cultured kidney cells with superexpression of the telomerase enzyme gene, which lengthens telomeres. In these cells with restored telomeres, the program of epithelial transition to the mesenchyma was normalized, and the cells returned to their healthy appearance before fibrosis.
Since telomeres in the cells of the body shorten as they age, it can be assumed that pathological EMT programs active in cancer and various types of tissue fibrosis can be triggered, at least partially, by the presence of short telomeres.
Article by S.Saraswati et al. Short and dysfunctional telomeres sensitize the kids to develop fibrosis is published in the journal Nature Aging.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to CNIO materials: CNIO researchers open the door to treatment of renal fibrosis by showing that it is caused by telomere shortening.