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A Novel Splice Variant of Human TGF-beta Type II Receptor Encodes a Soluble Protein and Its Fc-Tagged Version Prevents Liver Fibrosis in vivo
Journal article   Open access   Peer reviewed

A Novel Splice Variant of Human TGF-beta Type II Receptor Encodes a Soluble Protein and Its Fc-Tagged Version Prevents Liver Fibrosis in vivo

Marcela Soledad Bertolio, Anabela La Colla, Alejandra Carrea, Ana Romo, Gabriela Canziani, Stella Maris Echarte, Sabrina Campisano, German Patricio Barletta, Alexander Miguel Monzon, Tania Melina Rodriguez, …
Frontiers in cell and developmental biology, v 9, pp 690397-690397
10 Sep 2021
DOI: https://doi.org/10.3389/fcell.2021.690397
PMID: 34568316
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.3389/fcell.2021.690397View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Cell Biology Developmental Biology Life Sciences & Biomedicine Science & Technology
We describe, for the first time, a new splice variant of the human TGF-beta type II receptor (T beta RII). 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 beta RII-Soluble Endogenous (T beta RII-SE). Binding predictions indicate that the novel 13-amino-acid stretch interacts with all three TGF-beta cognate ligands and generates a more extensive protein-protein interface than T beta RII. T beta RII-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 beta RII-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 beta RII-SE/Fc is secreted as a disulfide-linked homodimer. Moreover, high-affinity binding of T beta RII-SE to the three TGF-beta isoforms was confirmed by surface plasmon resonance (SPR) analysis. Also, intrahepatic delivery of Lv.T beta RII-SE/Fc in a carbon tetrachloride-induced liver fibrosis model revealed amelioration of liver injury and fibrosis. Our results indicate that T beta RII-SE is a novel member of the TGF-beta signaling pathway with distinctive characteristics. This novel protein offers an alternative for the prevention and treatment of pathologies caused by the overproduction of TGF-beta ligands.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
Developmental Biology
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