title: HK2 Proximal Tubule Epithelial Cells Synthesize and Secrete Plasma Proteins Predominantly Through the Apical Surface.
abstract: Renal proximal tubule epithelial cells (PTECs) are known to reabsorb salts and small plasma proteins filtered through Bowman's capsule. Following acute kidney injury, PTECs assume some characteristics of hepatocytes in producing various plasma proteins. We now demonstrate that even at a resting state, a PTEC cell line, HK2 expresses mRNAs for and synthesizes and secretes plasma proteins in a complex with complement C3, an α2-macroglobulin family chaperone, including albumin, transferrin, α1-antitrypsin, α1-antichymotrypsin, α2-HS-glycoprotein, ceruloplasmin, haptoglobin, C1-inhibitor, secreted phosphoprotein-24, and insulin-like growth factor-1. When grown on transwell inserts, HK2 cells predominantly secrete (∼90%) plasma proteins into the apical side and a smaller fraction into the basolateral side as determined by ELISA assays. When cultured in the presence of exogenous cytokines such as IL1β, IL6, TNFα, BMP2, or TGFβ1, HK2 cell mRNA expressions for plasma proteins were variably affected whereas basolateral secretions were elevated to or in excess of those of the apical level. In addition, HK2 cells produce proTGFβ1 with its intact N-terminal latency associated peptide and latent-TGF-β-binding proteins. The complex cannot be dissociated under conditions of SDS, heating, and electrophoresis. Moreover, HK2 cells maintain their ability to quickly uptake exogenously added serum proteins from the culture medium, as if they are recognized differently by the endocytic receptors. These results provide new insight into the hepatization of PTECs. In addition to their unique uptake of plasma proteins and salts from the filtrate, they are a source of urinary proteins under normal conditions as wells as in chronic and acute kidney diseases. J. Cell. Biochem. 118: 924-933, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Geriatric Research, Education and Clinical Center (11E), Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda 91343, California.
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Zhao
authors.affiliation: Geriatric Research, Education and Clinical Center (11E), Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda 91343, California.|Department of Medicine, University of California, Los Angeles 90095, California.
authors.forename: Elsa J Brochmann
authors.initials: EJ
authors.lastname: Murray
authors.affiliation: Geriatric Research, Education and Clinical Center (11E), Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda 91343, California.|Department of Medicine, University of California, Los Angeles 90095, California.|Interdepartmental Program in Biomedical Engineering, University of California, Los Angeles 90095, California.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Murray
mesh_terms: D001693:Biological Transport, Active; D001798:Blood Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003176:Complement C3 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000096:biosynthesis / Q000235:genetics; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001798:Blood Proteins; C038245:C3 protein, human; D003176:Complement C3; D016207:Cytokines; D018836:Inflammation Mediators; D046912:Multiprotein Complexes; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: CHAPERONE; COMPLEMENT C3; CYTOKINES; HK2; HepG2; TGFβ; α2-MACROGLOBULIN (A2M)