{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:43:14Z","timestamp":1790624594204,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>We describe, for the first time, a new splice variant of the human TGF-\u03b2 type II receptor (T\u03b2RII). The new transcript lacks 149 nucleotides, resulting in a frameshift and the emergence of an early stop codon, rendering a truncated mature protein of 57 amino acids. The predicted protein, lacking the transmembrane domain and with a distinctive 13-amino-acid stretch at its C-terminus, was named T\u03b2RII-Soluble Endogenous (T\u03b2RII-SE). Binding predictions indicate that the novel 13-amino-acid stretch interacts with all three TGF-\u03b2 cognate ligands and generates a more extensive protein\u2013protein interface than T\u03b2RII. T\u03b2RII-SE and human IgG1 Fc domain were fused in frame in a lentiviral vector (Lv) for further characterization. With this vector, we transduced 293T cells and purified T\u03b2RII-SE\/Fc by A\/G protein chromatography from conditioned medium. Immunoblotting revealed homogeneous bands of approximately 37 kDa (reduced) and 75 kDa (non-reduced), indicating that T\u03b2RII-SE\/Fc is secreted as a disulfide-linked homodimer. Moreover, high-affinity binding of T\u03b2RII-SE to the three TGF-\u03b2 isoforms was confirmed by surface plasmon resonance (SPR) analysis. Also, intrahepatic delivery of Lv.T\u03b2RII-SE\/Fc in a carbon tetrachloride-induced liver fibrosis model revealed amelioration of liver injury and fibrosis. Our results indicate that T\u03b2RII-SE is a novel member of the TGF-\u03b2 signaling pathway with distinctive characteristics. This novel protein offers an alternative for the prevention and treatment of pathologies caused by the overproduction of TGF-\u03b2 ligands.<\/jats:p>","DOI":"10.3389\/fcell.2021.690397","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T01:54:33Z","timestamp":1631238873000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["A Novel Splice Variant of Human TGF-\u03b2 Type II Receptor Encodes a Soluble Protein and Its Fc-Tagged Version Prevents Liver Fibrosis in vivo"],"prefix":"10.3389","volume":"9","author":[{"given":"Marcela Soledad","family":"Bertolio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabela","family":"La Colla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Carrea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Romo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Canziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Maris","family":"Echarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Campisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German Patricio","family":"Barletta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Miguel","family":"Monzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania Melina","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Nancy","family":"Chisari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Alfredo","family":"Dewey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1080\/19420862.2015.1115166","article-title":"Development and characterization of human monoclonal antibodies that neutralize multiple TGF\u03b2 isoforms.","volume":"8","author":"Bedinger","year":"2016","journal-title":"mAbs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.tcb.2017.04.005","article-title":"Transforming growth factor-\u03b2 Recep-tors and Smads: regulatory complexity and functional versatility.","volume":"27","author":"Budi","year":"2017","journal-title":"Trends Cell Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ab.2003.11.004","article-title":"Kinetic screening of antibod-ies from crude hybridoma samples using Biacore.","volume":"325","author":"Canziani","year":"2004","journal-title":"Anal Biochem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.yexcr.2011.02.013","article-title":"Introduction to current and future protein therapeutics: a protein engineering perspective.","volume":"317","author":"Carter","year":"2011","journal-title":"Exp. 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