Biology subjects

Serrano Matos, Y. A.

Publications and source records attributed to Serrano Matos, Y. A..

3 recordsLinked to original sources

bioRxiv2025

NRF2-Dependent Anti-Inflammatory Activity of Indole via Cell Surface Receptor Signaling in Murine Macrophages

In this study, we report indoles anti-inflammatory effects to be AhR-independent in RAW 264.7 macrophages. To explore the possibility of indoles surface-receptor mediated signaling, we developed an indole-bovine serum albumin conjugate (I3B), which primarily engage cell surface receptors and has limited intracellular engagement. Treatment with 10 M of I3B led to a comparable reduction of TNF- production in LPS-stimulated RAW 264.7 macrophages to that observed with 500 M of free indole. Transcriptome profiling of I3B-treated LPS-stimulated RAW 264.7 macrophages revealed, I3B blunts pro-inflammatory response and induces gene signatures consistent with NRF2 activation. LPS-stimulated NRF2-/- Bone Marrow-derived Macrophages (BMM) treated with I3B, showed higher levels of pro-inflammatory cytokine production relative to non-treated BMM. To define the upstream pathways responsible for this NRF2-depedent response, we examined GPCR-mediated signaling and found that I3B engages a Gq-coupled receptor to induce PKC{delta} phosphorylation, and subsequent NRF2 phosphorylation. Our results suggest I3B signals through a surface-receptor in a NRF2-dependent manner to reduce inflammation in murine macrophages. TeaserA cell-impermeant indole conjugate inhibits inflammatory signaling in macrophages through an NRF2-dependent mechanism.

cell biology↗

bioRxiv2025

Maternal undernutrition exacerbates microbiota-driven growth stunting through pre and postnatal effects

Linear growth stunting due to undernutrition affects 20% of children under the age of five with far-reaching consequences, including increased susceptibility to infection and altered cognitive development. Current nutritional interventions are largely ineffective in rescuing linear growth. A significant proportion of stunting originates in utero; however, the mechanisms by which maternal undernutrition is transmitted between generations remain poorly characterized. Here we employed a gnotobiotic murine model of intergenerational undernutrition in which offspring are exposed to distinct microbial communities both in utero and after birth. We found that maternal undernutrition exacerbated offspring growth deficits in a microbiota-dependent manner. Maternal undernutrition also altered the offspring microbiome, increasing abundance of Enterococcus species and Escherichia coli. Cross-fostering demonstrated critical roles for the microbiota in growth during both gestation and early life. These findings emphasize the need to target both mother and child in the design of nutritional therapies for undernutrition.

microbiology↗

bioRxiv2023

Colonization during a key developmental window reveals microbiota-dependent shifts in growth and immunity during undernutrition

Childhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to undernutrition has been linked to poor outcomes, and mothers who experience stunting are more likely to give birth to stunted children. Murine models that capture the intergenerational and multifactorial nature of undernutrition are critical to understanding the underlying biology of this disorder. Here we report a gnotobiotic mouse model of undernutrition using microbiota from human infants with healthy or stunted growth trajectories. Intergenerational transmission of microbiota from parents to offspring leads to the development of growth and immune features of undernutrition and enteropathy, including reduced linear growth, intestinal villus blunting and accumulation of intraepithelial lymphocytes. In contrast, colonization after weaning reduces sensitivity to detect changes driven by distinct microbial communities. Overall, these results suggest intergenerational colonization is a useful approach with which to investigate microbiota-dependent growth and immunity in early life.

microbiology↗