Louisiana Via Research Day Book 2026

Biomedical Research: Section 1

Biomedical Research: Section 1

Julie Do, OMS-I; Ryan Vergara, OMS-III; Hunter Santogrossi, OMS-III; Dinesh Aryal, PhD VCOM-Louisiana 10 HEME OXYGENASE-1–DEPENDENT ACTIVATION OF TUBULAR NA + /H + EXCHANGER 3 UNDERLIES HYPERTENSION DURING CHRONIC METABOLIC ACIDOSIS

Erin Vasquez, OMS-III; Anne B. Remorca, OMS-III; Sabeen Wazir, OMS-III; Kasia Michalak, MSc; Stephen DiGiuseppe, PhD VCOM-Louisiana 9 POXVIRUSES REPROGRAM WNT/ ß -CATENIN SIGNALING THROUGH GSK-3 ß TO PROMOTE INFECTION

Background: Poxviruses such as mpox are re-emerging pathogens that pose a burden of disease. The glycogen synthase kinase-3ß (GSK-3ß) - ß-catenin axis regulates cell growth, Wnt signaling, and immune modulation. When GSK-3ß activity is reduced, ß-catenin escapes degradation and enters the nucleus to drive transcription of TCF/LEF target genes. Many viruses exploit this pathway by disrupting the destruction complex, stabilizing ß-catenin to enhance replication. However, our data reveals that poxviruses exhibit the opposite strategy. Vaccinia virus (VacV), a prototypic poxvirus, increases phosphorylated ß-catenin and accelerates its degradation. Notably, ß-catenin is critical to Wnt signaling, the pathway that contributes to the antiviral response; we reasoned that poxviruses target ß-catenin to suppress immunity. Hypothesis: We hypothesize that poxviruses utilize host GSK-3ß kinase to tag ß-catenin for degradation, inhibit Wnt signaling, and dampen the antiviral response to enhance replication.

of infection and time points, then measured viral titers and protein levels. Parallel cultures received selective GSK-3ß kinase inhibitors. We quantified total and phosphorylated ß-catenin by western blot and assessed viral proteins D8 and A14 by immunoblotting. Plaque assays determined the effect of GSK-3ß inhibition on replication. Results: Inhibition of GSK-3ß reversed infection-induced changes total ß-catenin increased, phosphorylated ß-catenin decreased, IRF3 was phosphorylated, and viral proteins and plaque formation were decreased. Conclusions: These results indicate poxviruses rely on GSK-3ß kinase activity to tag ß-catenin for degradation, suppress Wnt/ß-catenin signaling, and evade host antiviral defenses. Furthermore, this data identifies GSK-3ß as a potential therapeutic target.

Context: Heme oxygenase-1 (HO-1) produced in the kidney has recently been implicated in chronic metabolic acidosis (CMA), which itself has been associated with hypertension in murine models. However, the direct effects of CMA mediated through renal HO-1 on pressure natriuresis, and renal vascular function remain poorly understood. This study examined renal HO-1 expression during CMA and evaluated its influence on proximal tubular Na + /H + exchanger 3 (NHE3) expression and renal vasculature. Objective: To determine whether HO-1– dependent upregulation of renal tubular NHE3 promotes sodium retention and hypertension in a rat model of chronic metabolic acidosis. Methods: Male Sprague–Dawley rats (150–320 g) were assigned to four groups (n = 5/group) (I) Control, (II) CMA, (III) CMA + δ -aminolevulinic acid (DALA; HO-1 inducer), and (IV) CMA + zinc protoporphyrin IX (ZnPP; HO-1 inhibitor). CMA was induced using 0.28 M ammonium chloride for 8 weeks in Groups II–IV, with corresponding HO-1 modulation in Groups III and IV. Renal HO-1 concentrations in microdialysis samples, proximal tubular NHE3 expression, serum &

urine-sodium concentrations and renal blood flow (RBF) is measured.

Results: CMA significantly increased renal HO-1 levels and mean arterial pressure (MAP) compared with controls. However, HO-1 induction in the kidney appeared independent of circulating HO-1, as renal HO-1 levels did not differ between Groups III and IV. RBF remained unchanged across all groups, indicating an absence of renovascular hypertension. NHE3 expression is elevated in the CMA group and is significantly reduced in the HO-1 inhibited group (IV), consistent with impaired pressure natriuresis. Conclusions: Overall, these results lead to the findings that, renal HO-1 modulates proximal tubular NHE3 expression to maintain basal blood pressure and contributes to hypertension under chronic acidotic conditions.

Funding: This work was funded through Delta CRP grant (1032432).

Method: Normal human dermal fibroblasts were infected with VacV at varying multiplicities

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2026 Research Recognition Day