miRNA in airway diseases

SPINELLI, S.V.

Buenos Aires

Simposio; XVIII Jornadas Anuales Multidisciplinaria de la Sociedad Argentina de Biología ?Codificar o no codificar: rol de ARN no codificantes en la fisiología y la patología?; 2016

miRNAs are endogenous ~23 nt RNAs that play important gene-regulatory roles by pairing to the mRNAs of protein-coding genes to direct their post-transcriptional repression. These small molecules are involved in a wide range of physiological responses, including development, differentiation and homeostasis. Recent findings point out that miRNAs may also be involved in modulating corticosteroid sensitivity by regulating the expression of the active glucocorticoid receptor (hGR. Understanding the molecular mechanisms underlying resistance to corticosteroid is an essential requirement for the development of new therapeutic approaches. In tuberculosis, previews experiments performed in the lab showed that patients develop an imbalanced immune-endocrine response which may explain the increased inflammation and tissue destruction that occur during the course of the infection. Our studies comparing miRNA expression patterns in patients with active pulmonary tuberculosis and tuberculous pleurisy, a benign and self-limited form of the disease, showed that several miRNA are differentially expressed in infected individuals and identified miR-30c as a specific marker of pulmonary manifestations of tuberculosis potentially involved in modulating glucocorticoid sensitivity in these patients. Synthetic glucocorticoids are also employed as anti-inflammatory drugs for the treatment of many chronic inflammatory and immune diseases, being the most effective therapy for asthma yet relatively ineffective in chronic obstructive pulmonary disease. Additional studies are being performed in patients tending to identify miRNAs involved in modulating corticosteroid sensitivity in these airway diseases in order to find common regulatory features that could constitute new therapeutic targets with possible pharmacological applications.