LRG1 explained

Leucine-rich alpha-2-glycoprotein 1 is a protein which in humans is encoded by the gene LRG1.^[1]

Function

See also: TGF beta signaling pathway and R-SMAD. The leucine-rich repeat (LRR) family of proteins, including LRG1, have been shown to be involved in protein-protein interaction, signal transduction, and cell adhesion and development. LRG1 is expressed during granulocyte differentiation.^{[1] [2]}

LRG1 has been shown to be involved in promoting neovascularization (new blood vessel growth) through causing a switch in transforming growth factor beta (TGFbeta) signaling in endothelial cells. LRG1 binds to the accessory receptor endoglin and promotes signaling via the ALK1-Smad1/5/8 pathway.^[3]

Application

Levels of the LRG protein are markedly elevated in acute appendicitis and therefore could be used as a diagnostic aid.^[4]

LRG1 may be a potential therapeutic target for the treatment of diseases where there is aberrant neovascularization.^[3]

Circulating LRG1 levels are increased in many cancer patients and may be a useful biomarker. Inhibition of LRG1 normalises the tumor vasculature, improves the efficacy of cytotoxic and immune therapies,^[5] and restricts metastatic spread. ^[6]

LRG1 has been implicated in the pathogenesis of numerous diseases including cancer, eye disease, neurodegenerative disease, diabetes, lung and kidney disease^[7]

Further reading

• Li X, Miyajima M, Jiang C, Arai H . Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus . Neuroscience Letters . 413 . 2 . 141–144 . February 2007 . 17194537 . 10.1016/j.neulet.2006.11.039 . 54324280 .
• Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA . Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry . Journal of Proteome Research . 5 . 6 . 1493–1503 . June 2006 . 16740002 . 10.1021/pr050492k .
• Cummings C, Walder J, Treeful A, Jemmerson R . Serum leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay . Apoptosis . 11 . 7 . 1121–1129 . July 2006 . 16699948 . 10.1007/s10495-006-8159-3 . 39838086 .
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD . Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry . Journal of Proteome Research . 4 . 6 . 2070–2080 . 2006 . 16335952 . 1850943 . 10.1021/pr0502065 .
• Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y, Sugano S, Hirata T, Goto T, Matsunaga T, Hiyama E, Hayashi Y, Ando H, Suita S, Kaneko M, Sasaki F, Hashizume K, Ohnuma N, Nakagawara A . 6 . Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas . Oncogene . 23 . 35 . 5901–5911 . August 2004 . 15221005 . 10.1038/sj.onc.1207782 . free .
• Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wiśniewski JR . Screening for N-glycosylated proteins by liquid chromatography mass spectrometry . Proteomics . 4 . 2 . 454–465 . February 2004 . 14760718 . 10.1002/pmic.200300556 . 29261009 .
• Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A . 6 . The human plasma proteome: a nonredundant list developed by combination of four separate sources . Molecular & Cellular Proteomics . 3 . 4 . 311–326 . April 2004 . 14718574 . 10.1074/mcp.M300127-MCP200 . free .
• O'Donnell LC, Druhan LJ, Avalos BR . Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation . Journal of Leukocyte Biology . 72 . 3 . 478–485 . September 2002 . 12223515 . 10.1189/jlb.72.3.478 . 967662 . free .
• Saito K, Tanaka T, Kanda H, Ebisuno Y, Izawa D, Kawamoto S, Okubo K, Miyasaka M . 6 . Gene expression profiling of mucosal addressin cell adhesion molecule-1+ high endothelial venule cells (HEV) and identification of a leucine-rich HEV glycoprotein as a HEV marker . Journal of Immunology . 168 . 3 . 1050–1059 . February 2002 . 11801638 . 10.4049/jimmunol.168.3.1050 . free .
• Takahashi N, Takahashi Y, Putnam FW . Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum . Proceedings of the National Academy of Sciences of the United States of America . 82 . 7 . 1906–1910 . April 1985 . 3856868 . 397442 . 10.1073/pnas.82.7.1906 . free . 1985PNAS...82.1906T .
• Andersen JD, Boylan KL, Xue FS, Anderson LB, Witthuhn BA, Markowski TW, Higgins L, Skubitz AP . 6 . Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in-gel electrophoresis . Electrophoresis . 31 . 4 . 599–610 . January 2010 . 20162585 . 3520508 . 10.1002/elps.200900441 .

Notes and References

1. Web site: Entrez Gene: LRG1 leucine-rich alpha-2-glycoprotein 1.
2. O'Donnell LC, Druhan LJ, Avalos BR . Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation . Journal of Leukocyte Biology . 72 . 3 . 478–485 . September 2002 . 12223515 . 10.1189/jlb.72.3.478 . 967662 . free .
3. Wang X, Abraham S, McKenzie JA, Jeffs N, Swire M, Tripathi VB, Luhmann UF, Lange CA, Zhai Z, Arthur HM, Bainbridge J, Moss SE, Greenwood J . 6 . LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling . Nature . 499 . 7458 . 306–311 . July 2013 . 23868260 . 3836402 . 10.1038/nature12345 . 2013Natur.499..306W .
4. Web site: A urine test for appendicitis? . Vargas IM . 2009-06-23 . HarvardScience Press Release . Harvard College . 2009-06-25.
5. O'Connor MN, Kallenberg DM, Camilli C, Pilotti C, Dritsoula A, Jackstadt R, Bowers CE, Watson HA, Alatsatianos M, Ohme J, Dowsett L, George J, Blackburn JW, Wang X, Singhal M, Augustin HG, Ager A, Sansom OJ, Moss SE, Greenwood J . 6 . LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency . English . Med . 2 . 11 . 1231–1252.e10 . November 2021 . 35590198 . 10.1016/j.medj.2021.10.002 . 7614757 . free .
6. Singhal M, Gengenbacher N, Abdul Pari AA, Kamiyama M, Hai L, Kuhn BJ, Kallenberg DM, Kulkarni SR, Camilli C, Preuß SF, Leuchs B, Mogler C, Espinet E, Besemfelder E, Heide D, Heikenwalder M, Sprick MR, Trumpp A, Krijgsveld J, Schlesner M, Hu J, Moss SE, Greenwood J, Augustin HG . 6 . Temporal multi-omics identifies LRG1 as a vascular niche instructor of metastasis . Science Translational Medicine . 13 . 609 . eabe6805 . September 2021 . 34516824 . 10.1126/scitranslmed.abe6805 . 237402143 . 7614902 .
7. Camilli C, Hoeh AE, De Rossi G, Moss SE, Greenwood J . LRG1: an emerging player in disease pathogenesis . Journal of Biomedical Science . 29 . 1 . 6 . January 2022 . 35062948 . 8781713 . 10.1186/s12929-022-00790-6 . free .