Daiana Fornes

All Publications

• Loss of TRPV4 decreases NFκB-mediated myometrial inflammation and prevents preterm labor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Ingles, J. A., Rodriguez, Z., Fornes, D., Ying, L., Han, X., Cornfield, D. N., Alvira, C. M. 2025; 39 (4): e70418

  Abstract

  Inflammation is a key initiating event in both spontaneous term and preterm labor. However, the link between inflammation and the onset of labor remains incompletely understood. We identified the transient receptor potential vanilloid 4 (TRPV4) channel as a critical regulator of myometrial calcium (Ca2+) entry and contractility. In this study, we aimed to determine if the TRPV4 channel regulates uterine inflammation and its subsequent effects on myometrial contractility in experimental preterm labor. We demonstrated that global loss of TRPV4 protected mice against inflammation-induced preterm labor, decreased baseline myometrial contractility, and diminished lipopolysaccharide-stimulated increases in oxytocin-mediated contraction. Pharmacological inhibition of TRPV4 in human myometrial smooth muscle cells (SMC) blunted lipopolysaccharide (LPS)-induced activation of nuclear factor kappa-B (NFκB) and pro-inflammatory cytokine expression. In contrast, pharmacologic activation of TRPV4 augmented LPS-induced NFκB activation. Further, TRPV4-mediated NFκB activation was dependent on extracellular Ca2+ entry in myometrial SMC. Together, these data show that extracellular Ca2+ entry via TRPV4 potentiates NFκB-mediated inflammation and increases susceptibility to preterm labor. The ability of TRPV4 to modulate both myometrial inflammation and contractility, processes central to the onset of preterm and term labor, suggests that the TRPV4 channel may represent a novel therapeutic target for the treatment of premature birth.

  View details for DOI 10.1096/fj.202402949R

  View details for PubMedID 39989412

• Intracellular Calcium Response to Oxytocin in Uterine Smooth Muscle Cells From Patients With Uterine Atony. Anesthesia and analgesia Ansari, J. R., Fornes, D., Obiyo, L. T., Michel, G., Cornfield, D. N. 2024

  View details for DOI 10.1213/ANE.0000000000007240

  View details for PubMedID 39495660

• miR-203 modulates pregnant myometrium contractility via transient receptor potential vanilloid 4 channel expression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Ying, L., Fornes, D. D., Dobberfuhl, A. D., Ansari, J. R., Alvira, C. M., Cornfield, D. N. 2024; 38 (22): e70173

  Abstract

  Preterm labor is the leading cause of neonatal death and major morbidity but remains a poorly understood process with no effective tocolytic therapies. Recent work has identified the transient receptor potential vanilloid 4 (TRPV4) channel, a membrane calcium channel upregulated in uterine smooth muscle through gestation, as integral in the transition from quiescence to contraction in the gravid uterus. The present study builds upon these findings and investigates regulation of the TRPV4 channel during pregnancy in the murine and human uterus by micro-RNA 203 (miR-203). We find a progressive decrease in miR-203 expression during gestation, accompanied by a reciprocal increase in TRPV4 mRNA and protein expression. In human uterine smooth muscle cells (UtSMC), miR-203 overexpression reduces, and si-RNA-mediated silencing increases, TRPV4 expression. Studies using murine UtSMC demonstrate that miR-203 expression modulates TRPV4-mediated cytosolic calcium entry and contractility. Consistent with these findings, the response to pharmacologic TRVP4 agonists is increased in myometrial tissue from miRNA203 -/- mice compared to control mice. Moreover, we demonstrate that miR-203 binds specifically on the promoter region of TRPV4 to decrease expression. In murine inflammatory models of preterm labor, miR-203 overexpression prolongs pregnancy. Estradiol (E2) decreases miR-203 and increases TRPV4 expression, providing a potential physiologic link for the unique reciprocal relationship in UtSMC. Taken together, these findings provide evidence that miR-203 modulates uterine contractility during pregnancy via negative regulation of TRPV4. These findings support the hypothesis that targeting miR-203 holds the promise of an entirely novel approach to prevent prematurity and treat preterm labor.

  View details for DOI 10.1096/fj.202401783RR

  View details for PubMedID 39545721

• ROLE OF TRPV4 IN MODULATING CALCIUM SIGNALING PATHWAYS IN NON-LABORING PREGNANT WOMEN: IMPLICATIONS FOR MYOMETRIAL CONTRACTILITY AND PRETERM LABOR MANAGEMENT Fornes, D., Ying, L., Ansari, J., Obiyo, L., Alvira, C., Cornfield, D. W B SAUNDERS CO LTD. 2023: E33-E34

  View details for Web of Science ID 001069701600103

• Transient Receptor Potential Vanilloid 4 Channel Blockade Decreases Contractility of the Pregnant Human Myometrium Ying, L., Fornes, D., Obiyo, L. T., Ansari, J., Alvira, C. M., Cornfield, D. N. SPRINGER HEIDELBERG. 2023: 112A-113A

  View details for Web of Science ID 001043029500176