Development is a dynamic process characterized by critical periods in which organ systems are sensitive to changes in the surrounding environment. In the current study, critical windows of embryonic growth and kidney development were assessed in the embryonic chicken. All‐trans retinoic acid (tRA) influences not only organogenesis and cell proliferation, but also targets metanephric kidney nephrogenesis. Embryonic chickens were given a single injection of tRA on embryonic day 8. tRA decreased embryo, kidney, and heart mass from day 16 to day 18. However, mass specific kidney and heart masses showed no differences. Whole blood, plasma, and allantoic fluid osmolality were altered in tRA treated embryos from day 16 to day 18. In addition, hematocrit, red blood cell count, and hemoglobin concentration were altered in tRA treated embryos. The results suggest that although nephrogenesis was not affected by tRA, the developing osmoregulatory system was altered in tRA treated embryos.

Está bem estabelecido na literatura que o NHE3 é ativado, no intestino, pelo transporte de glicose mediado pelo SGLT1, e que esta ativação não dependente do metabolismo da glicose. Acredita-se que a co-ativação do NHE3 e do SGLT1 ocorra para maximizar a reabsorção de nutrientes no período pós-prandial. Porém, ainda não foi determinado se a captação de glicose através dos SGLTs é capaz de regular a atividade do NHE3 no túbulo proximal renal. Levando-se em conta que este segmento renal também expressa o SGLT2 e que os rins e intestinos apresentam significativas diferenças na disponibilidade de glicose ao longo do dia, o objetivo do presente trabalho foi o de determinar o efeito da glicose e da atividade dos SGLTs renais sobre a atividade do NHE3. Experimentos de microperfusão estacionária demonstraram que a perfusão luminal de glicose 5mM estimula o NHE3 via o metabolismo glicolítico. A perfusão de concentrações suprafisiológicas de glicose inibe o NHE3 por promover aumento de volume celular. A inibição farmacológica dos SGLTs, utilizando-se o inibidor inespecífico Florizina, ocasionou acentuada inibição do NHE3, mesmo na ausência de glicose. Além disso, experimentos de imunofluorescência determinaram que o NHE3 é co-expresso com o SGLT2, mas não com o SGLT1. Conclusão: os resultados deste trabalho demonstram que a glicose apresenta um efeito bimodal sobre o NHE3: em concentrações fisiológicas este açúcar estimula o NHE3, enquanto que em concentrações suprafisiológicas a glicose inibe o trocador. Além disso, a inibição farmacológica do transporte de glicose ocasiona acentuada inibição do NHE3 demonstrando que estes transportadores interagem funcionalmente no túbulo proximal. / It is well established that SGLT1-mediated glucose uptake leads to NHE3 activation in the intestine. This co-activation is thought to be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake is capable of regulating NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses another SGLT isoform, SGLT2, and that the kidneys and intestine show significant variations in daily glucose availability, the goal of the present work was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments demonstrated that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 due to cell swelling. Interestingly, the pharmacological inhibition of SGLT activity by phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 co-localizes with SGLT2, but not with SGLT1, in the rat renal proximal tubule. Collectively, the findings of this work demonstrate that glucose exerts a bimodal effect on NHE3. The physiological metabolism of glucose stimulates NHE3 transport activity, whereas supraphysiological glucose concentrations inhibit this exchanger. Additionally, phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.

In the yellow fever mosquito, Aedes aegypti (L.), hemolymph-circulating diuretic hormones act upon the renal organs (Malpighian tubules) to regulate primary urine composition and secretion rate; however, the molecular endocrine mechanisms underlying rapid water elimination upon adult eclosion and blood feeding are not fully understood. Bioinformatic analysis of the current Aedes aegypti genome assembly reveals only a single predicted corticotropin releasing factor (CRF)-like diuretic hormone 44 (DH44) gene, but two DH44 receptor genes. The tissue expression profiles of the DH44 receptor(s), and specifically the identity of the DH44 receptor(s) in the Malpighian tubule, are undetermined in any mosquito species. This dissertation shows that Vectorbase gene ID AAEL008292 encodes a DH44 receptor (AaegGPRdih1) transcribed in Malpighian tubules. Sequence analysis and transcript localization indicate that AaegGPRdih1 is the co-ortholog of the Drosophila melanogaster DH44 receptor (CG12370-PA). The presence of conserved amino acid residues between AaegGPRdih1 and vertebrate CRF receptors suggests this mosquito receptor modulates multiple G protein-dependent intracellular signaling pathways. Quantitative PCR analysis of a time course of Malpighian tubule cDNA reveals AaegGPRdih1 abundance increases paralleling periods of observed urination. This suggests that target tissue receptor biology is linked to the known periods of release of diuretic hormones from the nervous system, pointing to a common up-stream regulatory mechanism. Higher relative abundance of AaegGPRdih1 transcript in female Malpighian tubules 24 hours after blood feeding suggests a role for AaegGPRdih1 in the excretion of nitrogen waste. RNA-mediated silencing to establish the significance of AaegGPRdih1 to mosquito Malpighian tubule physiology was inconclusive.

Está bem estabelecido na literatura que o NHE3 é ativado, no intestino, pelo transporte de glicose mediado pelo SGLT1, e que esta ativação não dependente do metabolismo da glicose. Acredita-se que a co-ativação do NHE3 e do SGLT1 ocorra para maximizar a reabsorção de nutrientes no período pós-prandial. Porém, ainda não foi determinado se a captação de glicose através dos SGLTs é capaz de regular a atividade do NHE3 no túbulo proximal renal. Levando-se em conta que este segmento renal também expressa o SGLT2 e que os rins e intestinos apresentam significativas diferenças na disponibilidade de glicose ao longo do dia, o objetivo do presente trabalho foi o de determinar o efeito da glicose e da atividade dos SGLTs renais sobre a atividade do NHE3. Experimentos de microperfusão estacionária demonstraram que a perfusão luminal de glicose 5mM estimula o NHE3 via o metabolismo glicolítico. A perfusão de concentrações suprafisiológicas de glicose inibe o NHE3 por promover aumento de volume celular. A inibição farmacológica dos SGLTs, utilizando-se o inibidor inespecífico Florizina, ocasionou acentuada inibição do NHE3, mesmo na ausência de glicose. Além disso, experimentos de imunofluorescência determinaram que o NHE3 é co-expresso com o SGLT2, mas não com o SGLT1. Conclusão: os resultados deste trabalho demonstram que a glicose apresenta um efeito bimodal sobre o NHE3: em concentrações fisiológicas este açúcar estimula o NHE3, enquanto que em concentrações suprafisiológicas a glicose inibe o trocador. Além disso, a inibição farmacológica do transporte de glicose ocasiona acentuada inibição do NHE3 demonstrando que estes transportadores interagem funcionalmente no túbulo proximal. / It is well established that SGLT1-mediated glucose uptake leads to NHE3 activation in the intestine. This co-activation is thought to be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake is capable of regulating NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses another SGLT isoform, SGLT2, and that the kidneys and intestine show significant variations in daily glucose availability, the goal of the present work was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments demonstrated that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 due to cell swelling. Interestingly, the pharmacological inhibition of SGLT activity by phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 co-localizes with SGLT2, but not with SGLT1, in the rat renal proximal tubule. Collectively, the findings of this work demonstrate that glucose exerts a bimodal effect on NHE3. The physiological metabolism of glucose stimulates NHE3 transport activity, whereas supraphysiological glucose concentrations inhibit this exchanger. Additionally, phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.

Tendo em vista a importância do permutador Na+/H+ (isoforma 3) na reabsorção de NaCl e NaHCO3 em túbulos proximais e conseqüentemente no equilíbrio ácido-base e volume celular, surgiu o interesse em identificar a região promotora essencial para a transcrição do gene NHE3 e os elementos de ligação de fatores de transcrição presentes no mesmo, em células de túbulos proximais renais. Para isso, os segmentos da região flanqueadora 5´ do gene NHE3 de rato foram obtidos por PCR e inseridos no plasmídeo pGL3-basic, que codifica o gene repórter Firefly lucíferase. Os seguintes fragmentos foram analisados 1) -157 a +31; 2) -152 a +55; 3) -85 a +31; 4) -65 a +31; 5) -44 a +31; 6) -33 a +31; 7) -25 a +31; 8) -157 a +35, com deleção do elemento GATA (posição +20 a +23). Estes foram transfectados em células OKP, uma linhagem de túbulos proximais de rim de opossum. A atividade promotora de transcrição de cada segmento foi analisada em comparação com a atividade de luciferase observada com a transfecção do vetor pGL3-basic não recombinante, sem promotor. Foi realizado a cotransfecção do vetor pRL-CMV, que contém o gene da proteína repórter Renilla luciferase, usado como controle da eficiência de transfecção. Após serem analisados os resultados, observou-se que a atividade do promotor foi mais elevada com o constructo -152 a +55 (76.52 ± 45.26 (n=9)). Além disso, conseguimos identificar a existência de possíveis ativadores transcricionais no segmento entre a posição 85 e 65 (Egr-1/Sp1); 44 e 33 (Egr-1) e -33 e -25 (elemento TATA-Box não canônico), pois a remoção destes nucleotídeos reduziu significativamente a atividade do promotor. Outra observação foi a presença de elementos inibitórios entre as bases 65 e 44 (Sp1/Ap2), pois com a retirada destes, observamos um aumento muito significativo da atividade do promotor. O menor segmento (25/+31) apresentou atividade promotora significativa, sugerindo que ainda tenha os elementos indispensáveis para a montagem do complexo transcricional primário, embora com eficiência já bem reduzida. A presença do elemento GATA no primeiro exon, embora importante para a transcrição do gene NHE3 em células intestinais, não parece ser importante para a atividade transcricional em células de túbulos proximais. / In view of the importance of the exchanger Na+/H+ (isoform 3), in reabsoption of NaCl and NaHCO3 in proximal tubules and consequently the acid-base balance, and cell volume, came the interest in identifying the region promoter essential for transcription of the NHE3 gene and the elements of the binding of transcription factors present in the same, in cells renal proximal tubules. For this, segments of the 5 flanking region of the rat NHE3 gene were obtained by PCR and inserted into pGL3-basic vector, which encodes Firefly luciferase reporter gene. The following fragments were analyzed 1) -157 to +31, 2) -152 to +55, 3) -85 to +31, 4) -65 to +31, 5) -44 to +31, 6) -33 to +31, 7) -25 to +31; 8) -157 to +35, with deletion of the GATA element (position +20 to +23). These were transfected in OKP cells, line of the renal proximal tubules of opossum kidney. The promoter activity of transcription of each segment was analyzed in comparison with the luciferase activity observed with transfection of the pGL3-basic vector recombinant, without promoter. Was performed cotransfecção of PRL-CMV vector, containing the gene of the reporter protein Renilla luciferase, used as internal control of the efficiency of transfection. After analyzing the results, observed promoter activity was higher with the construct -152 to +55 (76.52 ± 45.26 (n = 9)). Furthermore, we identify the possible existence of transcriptional activators in the segment between position -85 and -65 (Egr-1/Sp1), -44 and -33 (EGR-1) and -33 and -25 (atypical TATA-box element) because the removal of these nucleotides significantly reduced the activity of the promoter. Another observation was the presence of inhibitory elements between bases -65 and -44 (Sp1/Ap2), because with the deletion of these, we observed a very significant increase in the activity of the promoter. The lower segment (-25 / +31) showed significant promoter activity, suggesting that still has the elements essential for transcriptiption complex assembly of the primary, in spite of with reduced efficiency well. The presence of the GATA element in the first exon, although important for the transcription of the NHE3 gene in intestinal cells, does not appear to be important for transcriptional activity in cells of proximal tubules.

Tendo em vista a importância do permutador Na+/H+ (isoforma 3) na reabsorção de NaCl e NaHCO3 em túbulos proximais e conseqüentemente no equilíbrio ácido-base e volume celular, surgiu o interesse em identificar a região promotora essencial para a transcrição do gene NHE3 e os elementos de ligação de fatores de transcrição presentes no mesmo, em células de túbulos proximais renais. Para isso, os segmentos da região flanqueadora 5´ do gene NHE3 de rato foram obtidos por PCR e inseridos no plasmídeo pGL3-basic, que codifica o gene repórter Firefly lucíferase. Os seguintes fragmentos foram analisados 1) -157 a +31; 2) -152 a +55; 3) -85 a +31; 4) -65 a +31; 5) -44 a +31; 6) -33 a +31; 7) -25 a +31; 8) -157 a +35, com deleção do elemento GATA (posição +20 a +23). Estes foram transfectados em células OKP, uma linhagem de túbulos proximais de rim de opossum. A atividade promotora de transcrição de cada segmento foi analisada em comparação com a atividade de luciferase observada com a transfecção do vetor pGL3-basic não recombinante, sem promotor. Foi realizado a cotransfecção do vetor pRL-CMV, que contém o gene da proteína repórter Renilla luciferase, usado como controle da eficiência de transfecção. Após serem analisados os resultados, observou-se que a atividade do promotor foi mais elevada com o constructo -152 a +55 (76.52 ± 45.26 (n=9)). Além disso, conseguimos identificar a existência de possíveis ativadores transcricionais no segmento entre a posição 85 e 65 (Egr-1/Sp1); 44 e 33 (Egr-1) e -33 e -25 (elemento TATA-Box não canônico), pois a remoção destes nucleotídeos reduziu significativamente a atividade do promotor. Outra observação foi a presença de elementos inibitórios entre as bases 65 e 44 (Sp1/Ap2), pois com a retirada destes, observamos um aumento muito significativo da atividade do promotor. O menor segmento (25/+31) apresentou atividade promotora significativa, sugerindo que ainda tenha os elementos indispensáveis para a montagem do complexo transcricional primário, embora com eficiência já bem reduzida. A presença do elemento GATA no primeiro exon, embora importante para a transcrição do gene NHE3 em células intestinais, não parece ser importante para a atividade transcricional em células de túbulos proximais. / In view of the importance of the exchanger Na+/H+ (isoform 3), in reabsoption of NaCl and NaHCO3 in proximal tubules and consequently the acid-base balance, and cell volume, came the interest in identifying the region promoter essential for transcription of the NHE3 gene and the elements of the binding of transcription factors present in the same, in cells renal proximal tubules. For this, segments of the 5 flanking region of the rat NHE3 gene were obtained by PCR and inserted into pGL3-basic vector, which encodes Firefly luciferase reporter gene. The following fragments were analyzed 1) -157 to +31, 2) -152 to +55, 3) -85 to +31, 4) -65 to +31, 5) -44 to +31, 6) -33 to +31, 7) -25 to +31; 8) -157 to +35, with deletion of the GATA element (position +20 to +23). These were transfected in OKP cells, line of the renal proximal tubules of opossum kidney. The promoter activity of transcription of each segment was analyzed in comparison with the luciferase activity observed with transfection of the pGL3-basic vector recombinant, without promoter. Was performed cotransfecção of PRL-CMV vector, containing the gene of the reporter protein Renilla luciferase, used as internal control of the efficiency of transfection. After analyzing the results, observed promoter activity was higher with the construct -152 to +55 (76.52 ± 45.26 (n = 9)). Furthermore, we identify the possible existence of transcriptional activators in the segment between position -85 and -65 (Egr-1/Sp1), -44 and -33 (EGR-1) and -33 and -25 (atypical TATA-box element) because the removal of these nucleotides significantly reduced the activity of the promoter. Another observation was the presence of inhibitory elements between bases -65 and -44 (Sp1/Ap2), because with the deletion of these, we observed a very significant increase in the activity of the promoter. The lower segment (-25 / +31) showed significant promoter activity, suggesting that still has the elements essential for transcriptiption complex assembly of the primary, in spite of with reduced efficiency well. The presence of the GATA element in the first exon, although important for the transcription of the NHE3 gene in intestinal cells, does not appear to be important for transcriptional activity in cells of proximal tubules.

Le tubule proximal participe à la diurèse en modifiant la composition de l'ultrafiltrat glomérulaire. Grâce à de nombreux transports transépithéliaux, il le glucose, les acides aminés et les protéines de bas poids moléculaires, ainsi que 80 % des ions HPO42- ou HCO3-, 60 % des ions Na+, Cl-, K+, Ca2+, 75 % de l’eau et 30 % des ions Mg2+ ultrafiltrés.Durant ma thèse, j'ai étudié les rôles physiologiques et physiopathologiques de deux protéines de transport exprimées dans le tubule proximal.Dans le cadre de ma première étude, j'ai évalué in vivo la fonction rénale de souris n'exprimant pas une protéine appelée Kir4.2, dont le rôle est inconnu. Nos résultats montrent que Kir4.2, associée à Kir5.1, forme un canal potassique basolatéral Kir4.2/Kir5.1 dans le tubule proximal. L'absence de Kir4.2 provoque chez la souris une acidose tubulaire proximale isolée, consécutive à une ammoniogénèse altérée. De fait, la perte de fonctionnalité de Kir4.2 pourrait être à l'origine d'acidoses tubulaires proximales isolées familiales idiopathiques.Dans le cadre de ma seconde étude, j'ai analysé in vitro la fonctionnalité d'un mutant pathogène de l'échangeur 2Cl-/H+ ClC-5 impliqué dans la maladie de Dent. Cette maladie, caractérisée par une protéinurie de bas poids moléculaire associées à divers troubles du tubule proximal, serait liée à un défaut d'acidification des endosomes précoces par ClC-5. Toutefois, le mutant de ClC-5 que nous avons étudié, converti en canal chlorure, acidifie autant les endosomes précoces que le ClC-5 sauvage. Surprenants, ces résultats suggèrent que la maladie de Dent puisse être causée par un défaut d'accumulation d'ions chlorure dans l'endosome. / The proximal tubule is involved in diuresis by modifying the content of the glomerular ultrafiltrate. Using a variety of transepithelial transports systems, it reabsorbs all ultrafiltrated glucose, amino-acids and low molecular weight proteins, as well as 80% of HPO42- and HCO3- ions, about 60% of Na+, Cl-, K+, and Ca2+ ions, 75% of water and 30% of Mg2+.During this thesis, I determined the physiological and physiopathological roles of two transport proteins present in proximal tubule. Firstly, I evaluated the renal function of mice invalidated for the Kir4.2 protein, whose role was undetermined. Our results show that Kir4.2, in association with Kir5.1, form a Kir4.2/Kir5.1 potassium channel at the basolateral membrane of proximal tubular cells. Furthermore, Kir4.2-null mice exhibit a reduced ammoniagenesis leading to an isolated proximal renal tubular acidosis. This study provides the gene encoding Kir4.2 as a candidate gene for the yet unexplained autosomal dominant isolated proximal renal tubular acidosis.Secondly, I evaluated in vitro the functional consequences of a pathogenic mutation of the 2Cl-/H+ exchanger ClC-5, involved in Dent’s disease. This disease, characterized by a low-molecular-weigth-proteinuria in the context of a general proximal tubule dysfunction, is currently thought to be due to an acidification defect of early endosomes linked to a loss of function of ClC-5. Surprisingly, our results show that ClC-5, converted into a chloride channel by this mutation, indeed acidifies the early endosomes as well as the ClC-5 wild-type. Thus, Dent’s disease may originate from a defect in the accumulation of chloride ions into the early endosomes.

As células mesangiais (CM) apresentam papel essencial na fisiologia glomerular normal, e alterações em seu fenótipo levam ao desenvolvimento de glomerulopatias. A fase tardia da glomerulopatia diabética é caracterizada por fibrose e morte por apoptose das CM. Portanto, a identificação de novos elementos envolvidos nas modificações patológicas das CM facilitaria a compreensão da fisiopatologia das doenças glomerulares. A família de genes ID está implicada em processos celulares distintos, como proliferação, diferenciação e apoptose. O presente estudo tem por finalidade investigar as interações do gene ID1, com o DNA e/ou proteínas, em CM humanas. Aqui demonstramos que Id1 interage com o fator de transcrição USF2, inibindo sua atividade transcricional. Adicionalmente, demonstramos que BMP-7 e Id1 antagonizam a morte celular induzida por TGF<font face=\"Symbol\">b-1 por inibir a atividade de USF2. Nossos dados apontam para uma nova via molecular portencialmente relevante para o melhor entendimento da patogênese das doenças renais crônicas. / Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerophaties. The late phase of diabetic glomerulopathy is characterized by fibrosis and death of MC. Thus, the identification of novel elements involved in these alterations would facilitate the comprehension of the pathophysiology of glomerular diseases. The ID (Inhibitors of DNA binding) family of genes has been implicated in diverse cellular processes, such as proliferation, differentiation, and apoptosis control. This study aims to investigate the interactions of ID1, with DNA or proteins, in human mesangial cells. We demonstrated that Id1 binds specifically to the transcription factor USF2. In addition, we show that BMP-7 and Id1 antagonize TGF<font face=\"Symbol\">b-1 induced death by inhibiting USF2 activity in human MC. In conclusion, our results point to a novel molecular path involved in the pathogenesis of glomerular diseases.

Reptiles are polyphyletic, and previous studies of renal anatomy and physiology in reptiles have covered a wide diversity of species of different phylogeny and habitat. To date, no study has examined the renal morphology and function of a group of closely related reptiles from different environments, yet this design has a number of advantages. Firstly, phylogenetic effects are reduced while adaptive specialisations in renal function or structure can be elucidated, and secondly, the variation in renal form and function between closely related species may be quantified in an effort to appreciate better the variation between more distantly related species. In this thesis, kidney morphology and renal function were studied in three Western Australian agamid lizards inhabiting environments differing in the availability of water. These key species were Pogona minor, Ctenophorus nuchalis and Ctenophorus salinarum. The renal anatomy of the three key lizards was characterised by determining glomerular diameter, volume density, surface area and number in each. Allometric relationships between kidney, colon and body mass were investigated in these and an additional 11 species of agamid lizard. Patterns of response to osmotic challenge were recorded by measuring renal variables such as urine flow rate, glomerular filtration rate and fractional reabsorption of filtrate among the three key species, and concurrent measurements of circulating arginine vasotocin in P. minor and C. nuchalis allowed the response of this hormone to homeostatic imbalance in these species to be gauged. The gross morphology and the glomerular characteristics of the kidneys was remarkably similar between species. Glomerular number and other characters varied as a function of body size rather than species, contrasting with reports in the literature suggesting that a given species has a particular number of glomeruli. ... Thus, kidney morphology is constrained among species and the response of each species to osmotic perturbation is similar. However, the mechanisms underlying antidiuresis and the hormonal control of this process differ subtly between species, and there is some evidence to suggest that P. minor is more adapted to a mesic environment than the other two lizards examined in this study. The hypothesis that renal form and function reflect the environment in which a lizard lives therefore receives partial support, although the reptilian bauplan is able to mitigate many of the forces that could potentially lead to renal specialisation.

As células mesangiais (CM) apresentam papel essencial na fisiologia glomerular normal, e alterações em seu fenótipo levam ao desenvolvimento de glomerulopatias. A fase tardia da glomerulopatia diabética é caracterizada por fibrose e morte por apoptose das CM. Portanto, a identificação de novos elementos envolvidos nas modificações patológicas das CM facilitaria a compreensão da fisiopatologia das doenças glomerulares. A família de genes ID está implicada em processos celulares distintos, como proliferação, diferenciação e apoptose. O presente estudo tem por finalidade investigar as interações do gene ID1, com o DNA e/ou proteínas, em CM humanas. Aqui demonstramos que Id1 interage com o fator de transcrição USF2, inibindo sua atividade transcricional. Adicionalmente, demonstramos que BMP-7 e Id1 antagonizam a morte celular induzida por TGF<font face=\"Symbol\">b-1 por inibir a atividade de USF2. Nossos dados apontam para uma nova via molecular portencialmente relevante para o melhor entendimento da patogênese das doenças renais crônicas. / Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerophaties. The late phase of diabetic glomerulopathy is characterized by fibrosis and death of MC. Thus, the identification of novel elements involved in these alterations would facilitate the comprehension of the pathophysiology of glomerular diseases. The ID (Inhibitors of DNA binding) family of genes has been implicated in diverse cellular processes, such as proliferation, differentiation, and apoptosis control. This study aims to investigate the interactions of ID1, with DNA or proteins, in human mesangial cells. We demonstrated that Id1 binds specifically to the transcription factor USF2. In addition, we show that BMP-7 and Id1 antagonize TGF<font face=\"Symbol\">b-1 induced death by inhibiting USF2 activity in human MC. In conclusion, our results point to a novel molecular path involved in the pathogenesis of glomerular diseases.