Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29382685", "kind": "science-record", "revision": 2, "content_hash": "sha256:bc78a41ae76820eecf2761d759bd6e7a346facf12558e44109392150fc6b1f24", "created_at": "2026-11-01T15:40:31Z", "updated_at": "2026-11-01T18:49:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction.", "doi": "10.1681/ASN.2017050479", "pmid": "29382685", "authors": ["Giulia Furini", "Nina Schroeder", "Linghong Huang", "David Boocock", "Alessandra Scarpellini", "Clare Coveney", "Elisa Tonoli", "Raghavendran Ramaswamy", "Graham Ball", "Claudia Verderio", "Timothy S Johnson", "Elisabetta A M Verderio"], "journal": "Journal of the American Society of Nephrology : JASN", "year": 2018, "abstract": "Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.", "claims": [{"id": "claim-target-result", "statement": "The statistical/proteomic method was SWATH mass spectrometry for unbiased analysis of the TG2 membrane interactome relative to the entire proteome after UUO; the source data were deposited in ProteomeXchange under identifier PXD008173. No numerical result for the registered target is reported in the abstract.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29382685", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry."}, {"asset": "source:pmid:29382685", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data have been deposited to the ProteomeXchange with identifier PXD008173."}, {"asset": "source:pmid:29382685", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The statistical/proteomic method was SWATH mass spectrometry for unbiased analysis of the TG2 membrane interactome relative to the entire proteome after UUO; the source data were deposited in ProteomeXchange under identifier PXD008173. 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