Differential Modulation of Matrix Metalloproteinases-2 and -7 in LAM/TSC Cells

Matrix metalloproteinase (MMP) dysregulation is implicated in several diseases, given their involvement in extracellular matrix degradation and cell motility. In lymphangioleiomyomatosis (LAM), a pulmonary rare disease, MMP-2 and MMP-9 have been detected at high levels in serum and urine. LAM cells, characterized by a mutation in the tuberous sclerosis complex (TSC)1 or TSC2, promote cystic lung destruction. The role of MMPs in invasive and destructive LAM cell capability has not yet been fully understood. We evaluated MMP-2 and MMP-7 expression, secretion, and activity in primary LAM/TSC cells that bear a TSC2 germline mutation and an epigenetic modification and depend on epidermal growth factor (EGF) for survival. 5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody. Both drugs reduced MMP-2 and MMP-7 secretion and activity during wound healing and decreased their expression in lung nodules of a LAM mouse model. In LAM/TSC cells, MMP-2 and MMP-7 are dependent on tuberin expression, cellular adhesion, and migration. MMPs appears sensitive to rapamycin and anti-EGFR antibody only during cellular migration. Our data indicate a complex and differential modulation of MMP-2 and MMP-7 in LAM/TSC cells, likely critical for lung parenchyma remodeling during LAM progression.

Interoceptive sensibility predicts the ability to infer others’ emotional states

Emotional sensations and inferring another’s emotional states have been suggested to depend on predictive models of the causes of bodily sensations, so-called interoceptive inferences. In this framework, higher sensibility for interoceptive changes (IS) reflects higher precision of interoceptive signals. The present study examined the link between IS and emotion recognition, testing whether individuals with higher IS recognize others’ emotions more easily and are more sensitive to learn from biased probabilities of emotional expressions. We recorded skin conductance responses (SCRs) from forty-six healthy volunteers performing a speeded-response task, which required them to indicate whether a neutral facial expression dynamically turned into a happy or fearful expression. Moreover, varying probabilities of emotional expressions by their block-wise base rate aimed to generate a bias for the more frequently encountered emotion. As a result, we found that individuals with higher IS showed lower thresholds for emotion recognition, reflected in decreased reaction times for emotional expressions especially of high intensity. Moreover, individuals with increased IS benefited more from a biased probability of an emotion, reflected in decreased reaction times for expected emotions. Lastly, weak evidence supporting a differential modulation of SCR by IS as a function of varying probabilities was found. Our results indicate that higher interoceptive sensibility facilitates the recognition of emotional changes and is accompanied by a more precise adaptation to emotion probabilities.