| Author |
Pérez-barriocanal, Fernando Cuesta, Cristina Lopez-novoa, José M. Oujo, Bárbara Pérez-roque, Lucía Núñez-gómez, Elena Langa, Carmen Ruiz-remolina, Laura Muñoz-félix, José M. Bernabeu, Carmelo Arévalo, Miguel |
| Description |
Author Affiliation: Muñoz-Félix JM ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Pérez-Roque L ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Núñez-Gómez E ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Oujo B ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Arévalo M ( Department of Human Anatomy and Histology, Universidad de Salamanca, 37007 Salamanca, Spain.); Ruiz-Remolina L ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Cuesta C ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Langa C ( Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.); Pérez-Barriocanal F ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain); Bernabeu C ( Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.); Lopez-Novoa JM ( Renal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain) |
| Abstract |
Transforming growth factor beta 1 (TGF-β1) is one of the most studied cytokines involved in renal tubulo-interstitial fibrosis, which is characterized by myofibroblast abundance and proliferation, and high buildup of extracellular matrix in the tubular interstitium leading to organ failure. Endoglin (Eng) is a 180-kDa homodimeric transmembrane protein that regulates a great number of TGF-β1 actions in different biological processes, including ECM synthesis. High levels of Eng have been observed in experimental models of renal fibrosis or in biopsies from patients with chronic kidney disease. In humans and mice, two Eng isoforms are generated by alternative splicing, L-Eng and S-Eng that differ in the length and composition of their cytoplasmic domains. We have previously described that L-Eng overexpression promotes renal fibrosis after unilateral ureteral obstruction (UUO). However, the role of S-Eng in renal fibrosis is unknown and its study would let us analyze the possible function of the cytoplasmic domain of Eng in this process. For this purpose, we have generated a mice strain that overexpresses S-Eng (S-ENG $^{+}$ ) and we have performed an UUO in S-ENG $^{+}$ and their wild type (WT) control mice. Our results indicate that obstructed kidney of S-ENG $^{+}$ mice shows lower levels of tubulo-interstitial fibrosis, less inflammation and less interstitial cell proliferation than WT littermates. Moreover, S-ENG $^{+}$ mice show less activation of Smad1 and Smad2/3 pathways. Thus, S-Eng overexpression reduces UUO-induced renal fibrosis and some associated mechanisms. As L-Eng overexpression provokes renal fibrosis we conclude that Eng-mediated induction of renal fibrosis in this model is dependent on its cytoplasmic domain. |
