Biology subjects

Andrade, C. B. V.

Publications and source records attributed to Andrade, C. B. V..

3 recordsLinked to original sources

bioRxiv2026

Unravelling the memory of the extracellular matrix using MASH-derived decellularized scaffolds

The use of decellularized diseased livers in regenerative medicine is a promising approach for eliminating organ shortages. Bioengineering studies have shown that ECM can impact cell physiology, inducing cell activation, function, and ECM deposition, which suggests that the ECM has a "memory" that is involved in the outcome after recellularization. However, the effect of diseased ECM memory on new cells in vitro and in vivo has not been thoroughly investigated. Since it has been increasingly recognized that liver ECM changes due to different factors, it is comprehensively that diseased ECM obtained from discarded organs will ensure a distinct environment and impact cell survival and physiology. Thus, we aimed at investigating the impact of the memory of diseased ECM obtained from metabolic dysfunction-associated steatohepatitis (MASH)-derived organs on steatohepatitis establishment. To address this aim, we explored decellularized ECM obtained from rats and humans with MASH in different contexts. First, MASH ECM was characterized and then submitted to transplantation to investigate whether a MASH-derived ECM could be used as a scaffold for transplantation and to promote steatohepatitis features in control animals. Histological analysis revealed that the MASH-ECM was completely recellularized after transplantation in both control and MASH recipient rats. However, steatosis and fibrosis were observed in MASH ECM after transplantation in both groups. Molecular analysis showed that MASH ECM stimulates de novo lipogenesis and fibrosis 30 days after transplantation. Untargeted metabolomic analysis revealed that cells grown on MASH ECM had a similar metabolic profile, even when transplanted into healthy or MASH recipient rats. In addition, we observed that MASH ECM promoted impaired lipid oxidation and mitochondrial dysfunction when transplanted into healthy recipients. Altered lipid turnover and inflammatory signaling were observed in MASH ECM transplanted in MASH recipients. In vitro analysis revealed that MASH ECM induced lipid accumulation in HepG2 cells after 10 days of culture. Calcium signalling experiments obtained from HepG2 cells cultured in MASH ECM showed a lower response to ATP, a reduced calcium signalling amplitude, and a distinct response profile than that observed in healthy ECM. On the other hand, a diseased human-derived ECM could still provide an environment that allows cell development. Taken together, our data showed that MASH ECM impacts cell metabolism, promoting steatohepatitis maintenance. In conclusion, our data confirm that diseased ECM memory can impact cell physiology contributing to disease progression.

physiology↗

bioRxiv2023

Sex-specific effect of antenatal Zika virus infection on murine fetal growth, placental nutrient transporters, and nutrient sensor signaling pathways

Maternal Zika virus (ZIKV) infection during pregnancy can associate with severe intrauterine growth restriction (IUGR), placental damage, and metabolism disturbance, as well as newborn neurological abnormalities. Here, we investigated whether maternal ZIKV infection affects placental nutrient transporters and nutrient-sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU-ZIKVPE243) and High (5x107 PFU-ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, for tissue collection at GD18.5 (term). Feto-placental growth of male fetuses was dramatically affected by ZIKV, whereas no differences were observed in female fetuses. ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose-6-phosphate in female placentas, with no differences in amino-acid transport potential. In contrast, glucose transport in male placentas was not affected by ZIKV, whilst a decreased placental protein expression of sodium-coupled neutral amino acid 2 (Snat2) was detected in the male low-dose ZIKV-infected group. There were also sex-dependent differences in the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation in ZIKV infected pregnancies, showing that ZIKV can cause disturbance in the nutrient handling in the placental tissue. Our findings thus identify relevant molecular alterations in the placenta caused by maternal ZIKV infection related to nutrient transport and availability. Notably, our results suggest that female and male placentas adopt different strategies to cope with the altered metabolic state caused by ZIKV. This may have relevance for understanding the effects of congenital Zika syndrome and could potentially assist future therapeutic strategies. Author SummaryThe Zika virus (ZIKV) has emerged as a major global health concern in the past decade. ZIKV infection during pregnancy can cause infants to be born with microcephaly and fetal growth restriction, among other pregnancy complications. Currently, the number of cases of ZIKV disease declined onwards globally. However, transmission persists at low levels in several countries in the Americas and other endemic regions, with neither a licensed vaccine nor an antiviral drug available for prevention and treatment. Here, we use a mice model of maternal ZIKV infection to analyze placental nutrient transporters and nutrient-sensitive pathways as a potential link to the complications related to congenital ZIKV infection. We found that feto-placental growth of male fetuses was dramatically affected by ZIKV, whereas no differences were observed in female fetuses. We also found that placental nutrient transporters and nutrient-sensitive pathways were altered in response to ZIKV infection, depending on the fetal sex. Our study presents relevant molecular alterations caused by maternal ZIKV infection and suggests that female and male placentas adopt different strategies in response to the altered environment caused by ZIKV. Our observations may have relevance for understanding the effects of ZIKV infection and could potentially assist future therapeutic strategies.

physiology↗

bioRxiv2020

ZIKV disrupts fetal outcome, placental ultrastructure and drug transporter expression in mice

Congenital Zika virus (ZIKV) infection can induce fetal brain abnormalities. Here, we investigated whether maternal ZIKV infection affects placental physiology and metabolic transport potential and impacts the fetal outcome, regardless of viral presence in the fetus at term. Low (103 PFU-ZIKVPE243; low ZIKV) and high (5x107 PFU-ZIKVPE243; high ZIKV) virus titers were injected into immunocompetent (ICompetent C57BL/6) and immunocompromised (ICompromised A129) mice at gestational day (GD) 12.5 for tissue collection at GD18.5 (term). High ZIKV elicited fetal death rates of 66% and 100%, whereas low ZIKV induced fetal death rates of 0% and 60% in C57BL/6 and A129 dams, respectively. All surviving fetuses exhibited intrauterine growth restriction (IUGR) and decreased placental efficiency. High-ZIKV infection in C57BL/6 and A129 mice resulted in virus detection in maternal spleens and placenta, but only A129 fetuses presented virus RNA in the brain. Nevertheless, pregnancies in both strains produced fetuses with decreased head sizes (p<0.05). Low-ZIKV-A129 dams had higher IL-6 and CXCL1 levels (p<0.05), and their placentas showed increased CCL-2 and CXCL-1 contents (p<0.05). In contrast, low-ZIKV-C57BL/6 dams had an elevated CCL2 serum level and increased type I and II IFN expression in the placenta. Notably, less abundant microvilli and mitochondrial degeneration were evidenced in the placental labyrinth zone (Lz) of ICompromised and high-ZIKV-ICompetent mice but not in low-ZIKV-C57BL/6 mice. In addition, decreased placental expression of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and the lipid transporter Abca1 was detected in all ZIKV-infected groups, but Bcrp and Abca1 were only reduced in ICompromised and high-ZIKV ICompetent mice. Our data indicate that gestational ZIKV infection triggers specific proinflammatory responses and affects placental turnover and transporter expression in a manner dependent on virus concentration and maternal immune status. Placental damage may impair proper fetal-maternal exchange function and fetal growth/survival, likely contributing to congenital Zika syndrome.

physiology↗