Molecular and Cellular Endocrinology最新文献

{"title":"The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity","authors":"Daniela Rosendo-Silva ,&nbsp;Eduardo Lopes ,&nbsp;Tamaeh Monteiro-Alfredo ,&nbsp;Inês Falcão-Pires ,&nbsp;Hans Eickhoff ,&nbsp;Sofia Viana ,&nbsp;Flávio Reis ,&nbsp;Ana Salomé Pires ,&nbsp;Ana Margarida Abrantes ,&nbsp;Maria Filomena Botelho ,&nbsp;Raquel Seiça ,&nbsp;Paulo Matafome","doi":"10.1016/j.mce.2024.112367","DOIUrl":"10.1016/j.mce.2024.112367","url":null,"abstract":"<div><h3>Objective</h3><p>Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes.</p></div><div><h3>Methods</h3><p>The expression of the NPY/melanocortin receptors’ levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system.</p></div><div><h3>Results</h3><p>In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the <em>Lepr</em>-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity.</p></div><div><h3>Conclusions</h3><p>Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112367"},"PeriodicalIF":3.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0303720724002235/pdfft?md5=8003c570e08e4f3b3cd002fd1ac03bbb&pid=1-s2.0-S0303720724002235-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of miR-483-3p and miR-630 expression profile in pediatric adrenocortical tumors and the effect of their modulation on adrenal tumorigenesis in vitro","authors":"Carolina Alves Pereira Corrêa ,&nbsp;Augusto Faria Andrade ,&nbsp;Luciana Chain Veronez ,&nbsp;Keteryne Rodrigues da Silva ,&nbsp;Mirella Baroni ,&nbsp;Veridiana Kill Suazo ,&nbsp;Rosane de Paula Gomes Queiroz ,&nbsp;Régia Caroline Peixoto Lira ,&nbsp;Pablo Shimaoka Chagas ,&nbsp;Silvia Regina Brandalise ,&nbsp;José Andres Yunes ,&nbsp;Carlos Augusto Fernandes Molina ,&nbsp;Sonir Roberto Rauber Antonini ,&nbsp;Elvis Terci Valera ,&nbsp;Luiz Gonzaga Tone ,&nbsp;Carlos Alberto Scrideli","doi":"10.1016/j.mce.2024.112371","DOIUrl":"10.1016/j.mce.2024.112371","url":null,"abstract":"<div><p>Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and outcomes of several types of cancer. However, the role played by miRNAs in pediatric ACT has been poorly explored. In this study, we have evaluated the expression of miR-483-3p and miR-630 in 67 pediatric ACT and 19 non-neoplastic adrenal samples, the effects of the modulations of these miRNAs, and their relationship with the TGF-β pathway in the H295R and H295A cell lines. Deregulation of both miRNAs was related to survival and disease advanced stages and hence to patients’ prognosis. Moreover, modified miR-483-3p and miR-630 <em>in vitro</em> expression decreased cell viability and colony formation capacity, changed how some genes of the TGF-β pathway, such as <em>TGFBR1</em>, <em>TGFBR2</em>, and <em>SMAD7</em>, are expressed, and altered Smad3, pSmad3, Smad 2/3, N-cadherin, and Vimentin protein expression. Besides that, when inhibition of the TGF-β pathway was combined with miR-630 overexpression or miR-483-3p silencing, cell viability and colony formation capacity decreased, and protein expression in the TGF-β pathway changed. Together, the data indicate that both miRNAs participate in the TGF-β pathway and are therefore potential markers for predicting the prognosis of patients with pediatric ACT.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112371"},"PeriodicalIF":3.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex hormones and life histories: An evolutionary perspective","authors":"Gustavo M. Somoza, Vance L. Trudeau","doi":"10.1016/j.mce.2024.112372","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112372","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"118 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperthyroidism keeps immunoglobulin levels but reduces milk fat and CD11b/c+ cells on early lactation","authors":"María Belén Sánchez ,&nbsp;María Cecilia Michel Lara ,&nbsp;Flavia Judith Neira ,&nbsp;Claudio Rodríguez-Camejo ,&nbsp;Juan Manuel Ríos ,&nbsp;Luciana Belén Viruel ,&nbsp;María Tamara Moreno-Sosa ,&nbsp;Elisa Olivia Pietrobon ,&nbsp;Marta Soaje ,&nbsp;Graciela Alma Jahn ,&nbsp;Ana Hernández ,&nbsp;Susana Ruth Valdez ,&nbsp;Juan Pablo Mackern-Oberti","doi":"10.1016/j.mce.2024.112370","DOIUrl":"10.1016/j.mce.2024.112370","url":null,"abstract":"<div><p>Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T₄ (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRβ1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45⁺ and CD3⁺ cells and decreased CD11b/c⁺ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112370"},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex hormones and life histories: An evolutionary perspective","authors":"Gustavo M. Somoza,&nbsp;Vance L. Trudeau","doi":"10.1016/j.mce.2024.112369","DOIUrl":"10.1016/j.mce.2024.112369","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112369"},"PeriodicalIF":3.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear translocation of the membrane oxoeicosanoid/androgen receptor, OXER1: Possible mechanisms involved","authors":"Panagiotis Malamos ,&nbsp;Konstantina Kalyvianaki ,&nbsp;Athanasios A. Panagiotopoulos ,&nbsp;Amalia P. Vogiatzoglou ,&nbsp;Athanasia Artemis Tsikalaki ,&nbsp;Anastasia Katifori ,&nbsp;Hara Polioudaki ,&nbsp;Maria N. Darivianaki ,&nbsp;Panayiotis A. Theodoropoulos ,&nbsp;Christos A. Panagiotidis ,&nbsp;George Notas ,&nbsp;Elias Castanas ,&nbsp;Marilena Kampa","doi":"10.1016/j.mce.2024.112357","DOIUrl":"10.1016/j.mce.2024.112357","url":null,"abstract":"<div><p>OXER1, the receptor for the arachidonic acid metabolite 5-οxo-eicosatetraenoic acid (5-oxo-ETE), has been reported to also bind and mediate the membrane-initiated actions of androgens. Indeed, androgens antagonize the 5-oxo-ETE effects through OXER1, affecting a number of signaling pathways and inhibiting cancer cell proliferation and migration. OXER1, being a GPCR, was classically described to be localized in the plasma membrane. However, for numerous GPCRs, there is now strong evidence that they can be also found in other cellular compartments, including the nucleus. The aim of the present work was to investigate OXER1's possible localization in the nucleus and identify the mechanism(s) involved. For this purpose, we verified OXER1's nuclear presence by immunofluorescence and western blot, in whole cells and nuclei of two different prostate cancer cell lines (DU-145 and LNCaP) and in CHO cells transfected with a GFP labelled OXER1, both in untreated and OXER1 ligands' treated cells. Mutated, OXER1-tGFP expressing, CHO cells were used to verify that OXER1 agonist (5-oxo-ETE) binding is necessary for OXER1 nuclear translocation. NLS sequences were in silico identified, and a specific inhibitor, as well as, specific importins' siRNAs were also utilized to explore the mechanism involved. Moreover, we examined the role of palmitoylation in OXER1 nuclear translocation by in silico identifying possible palmitoylation sites and using a palmitoylation inhibitor. Our results clearly show that OXER1 can be localized in the nucleus, in an agonist-dependent manner, that is inhibited by androgens. We also provide evidence for two possible mechanisms for its nuclear trafficking, that involve receptor palmitoylation and importin-mediated cytoplasmic-nuclear transport. In our knowledge, it is the first time that a membrane androgen receptor is identified into the nucleus, suggesting an alternative, more direct, mode of action, involving nuclear mechanisms. Therefore, our findings provide new insights on androgen-mediated actions and androgen-lipid interactions, and reveal new possible therapeutic targets, not only for cancer, but also for other pathological conditions in which OXER1 may have an important role.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112357"},"PeriodicalIF":3.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hepatokine FGF21 stopped lipogenesis and reduced testosterone production in mLTC-1 Leydig Cell Line","authors":"Guillaume Bourdon ,&nbsp;Claire Chevaleyre ,&nbsp;Anthony Estienne ,&nbsp;Christine Péchoux ,&nbsp;Jérôme Bourgeais ,&nbsp;Olivier Hérault ,&nbsp;Mouhamadou Ba ,&nbsp;Christelle Ramé ,&nbsp;Joëlle Dupont ,&nbsp;Pierre-Henri Ducluzeau ,&nbsp;Pascal Froment","doi":"10.1016/j.mce.2024.112350","DOIUrl":"10.1016/j.mce.2024.112350","url":null,"abstract":"<div><p>Beyond their link to metabolic issues like type 2 diabetes, factors like lifestyle, environment, and excess weight may also influence fertility. Fibroblast growth factor 21 (FGF21), a liver-derived hormone linked to energy balance, has recently emerged as a potential player in female mammalian reproduction. In male, only two studies have described potential effects of FGF21 on fertility. A recent study has described a negative correlation observed in obese patients presenting a low testosterone level associated with elevated FGF21 plasma levels. To investigate the role of FGF21 in steroidogenesis, we have studied the involvement of FGF21 in lipid and steroid activity by Leydig cells.</p><p>Leydig cell model expressed all FGF21 receptors and β-Klotho cofactor as determined by RT-qPCR and by western-blot. Cultured mLTC-1 Leydig cell line exposed to increasing FGF21 concentration induced phosphorylation (Ser 473) of Akt and modified the CREB factor activity, suggesting the functionality of the FGF21 pathway.</p><p>FGF21 consequences on mLTC-1 Leydig cells are inhibition of the lipid synthesis, leading to a reduction in the content of lipid droplets. The drop in lipid synthesis is associated with a reduction in the amount of lipids (mainly PUFA, cholesterol esterified, and triglycerides) as measured by lipidomic approach. The main consequence is to reduce the quantity of cholesterol, the steroid precursor, in mLTC-1 Leydig cells and is associated with a low production in testosterone. The decrease in androgens was also associated with a reduction in the steroid enzyme genes expression, which are under the control of CREB activity, and present a lower activity due to low cAMP intracellular levels.</p><p>In vivo, steroid production was lowering after FGF21 administration in adult male mice associated to a decrease in progressive motility and velocity of sperm. In addition, these experimental data are reinforced by a data mining analysis focused on “gonad“ terms in 1,319,905 article references showing the link already described between FGF21 with the fatty acids pathways, cholesterol storage, and steroid production.</p><p>In conclusion, we demonstrated that Leydig cells in the testes present a functional FGF21 pathway, which regulates lipid metabolism and steroid function. In mLTC-1 Leydig cells, FGF21 reduced cholesterol, PUFA content, and testosterone production. Finally, this work highlighted that the hepatokine FGF21 could have a negative impact on androgen synthesis and testicular activity.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112350"},"PeriodicalIF":3.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0303720724002065/pdfft?md5=37fbf93c5f96b11fa792d7d78629cbde&pid=1-s2.0-S0303720724002065-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paricalcitol prevents renal tubular injury induced by ischemia-reperfusion: Role of oxidative stress, inflammation and AT1R","authors":"Marry Aneyts de Santana Cirilo ,&nbsp;Fernanda Priscila Barbosa Ribeiro ,&nbsp;Natália Kryzia dos Santos Lima ,&nbsp;Jeoadã Karollyne Silva ,&nbsp;José Anderson da Silva Gomes ,&nbsp;Jéssica Santos Schirato Albuquerque ,&nbsp;Lucas Cristiano da Silva Siqueira ,&nbsp;Valéria Bianca de Souza Santos ,&nbsp;Jennyfer Martins de Carvalho ,&nbsp;Fernanda das Chagas Angelo Mendes Tenorio ,&nbsp;Leucio Duarte Vieira","doi":"10.1016/j.mce.2024.112349","DOIUrl":"10.1016/j.mce.2024.112349","url":null,"abstract":"<div><p>The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na⁺ transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (AT₁R). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na⁺ transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and AT₁R. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/AT₁R signaling.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112349"},"PeriodicalIF":3.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic pheochromocytoma and paraganglioma: Integrating tumor biology in clinical practice","authors":"Jeena Varghese ,&nbsp;Catherine M. Skefos ,&nbsp;Camilo Jimenez","doi":"10.1016/j.mce.2024.112344","DOIUrl":"10.1016/j.mce.2024.112344","url":null,"abstract":"<div><p>Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells in the autonomic nervous system. Depending on their location, these tumors are capable of excessive catecholamine production, which may lead to uncontrolled hypertension and other life-threatening complications. They are associated with a significant risk of metastatic disease and are often caused by an inherited germline mutation.</p><p>Although surgery can cure localized disease and lead to remission, treatments for metastatic PPGL (mPPGL)—including chemotherapy, radiopharmaceutical agents, multikinase inhibitors, and immunotherapy used alone or in combination— aim to control tumor growth and limit organ damage.</p><p>Substantial advances have been made in understanding hereditary and somatic molecular signaling pathways that play a role in tumor growth and metastasis. Treatment options for metastatic disease are rapidly evolving, and this paper aims to provide a brief overview of the management of mPPGL with a focus on therapy options.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"592 ","pages":"Article 112344"},"PeriodicalIF":3.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan","authors":"Matheus Naia Fioretto ,&nbsp;Flávia Alessandra Maciel ,&nbsp;Luísa Annibal Barata ,&nbsp;Isabelle Tenori Ribeiro ,&nbsp;Carolina Beatriz Pinheiro Basso ,&nbsp;Marcel Rodrigues Ferreira ,&nbsp;Sérgio Alexandre Alcantara dos Santos ,&nbsp;Renato Mattos ,&nbsp;Hecttor Sebastian Baptista ,&nbsp;Luiz Marcos Frediane Portela ,&nbsp;Pedro Magalhães Padilha ,&nbsp;Sérgio Luis Felisbino ,&nbsp;Wellerson Rodrigo Scarano ,&nbsp;Elena Zambrano ,&nbsp;Luis Antonio Justulin","doi":"10.1016/j.mce.2024.112348","DOIUrl":"10.1016/j.mce.2024.112348","url":null,"abstract":"<div><p>The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"592 ","pages":"Article 112348"},"PeriodicalIF":3.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}