Next Article in Journal
Chemical Constituents from Apios americana and Their Inhibitory Activity on Tyrosinase
Previous Article in Journal
HnRNPA1 Specifically Recognizes the Base of Nucleotide at the Loop of RNA G-Quadruplex
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Molecules 2018, 23(1), 200; https://doi.org/10.3390/molecules23010200

Tamm–Horsfall Protein is a Potent Immunomodulatory Molecule and a Disease Biomarker in the Urinary System

1
Division of Nephrology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan
2
Division of Rheumatology, Immunology & Allergy, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
3
Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital and National Yang-Ming University, 201 Shih-Pai Road, Sec 2, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Received: 20 December 2017 / Revised: 17 January 2018 / Accepted: 17 January 2018 / Published: 22 January 2018
Full-Text   |   PDF [1099 KB, uploaded 22 January 2018]   |  

Abstract

Tamm–Horsfall protein (THP), or uromodulin (UMOD), is an 80–90-kDa phosphatidylinositol-anchored glycoprotein produced exclusively by the renal tubular cells in the thick ascending limb of the loop of Henle. Physiologically, THP is implicated in renal countercurrent gradient formation, sodium homeostasis, blood pressure regulation, and a defense molecule against infections in the urinary system. Investigations have also revealed that THP is an effective binding ligand for serum albumin, immunoglobulin G light chains, complement components C1 and C1q, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and interferon-γ through its carbohydrate side chains for maintaining circulatory and renal immune homeostasis. Thus, THP can be regarded as part of the innate immune system. UMOD mutations play crucial roles in congenital urolithiasis, hereditary hyperuricemia/gout, and medullary cystic kidney diseases. Recent investigations have focused on the immunomodulatory effects of THP on immune cells and on THP as a disease biomarker of acute and chronic kidney diseases. Our studies have suggested that normal urinary THP, through its epidermal growth factor (EGF)-like domains, binds to the surface-expressed EGF-like receptors, cathepsin G, or lactoferrin to enhance polymorphonuclear leukocyte phagocytosis, proinflammatory cytokine production by monocytes/macrophages, and lymphocyte proliferation by activating the Rho family and mitogen-activated protein kinase signaling pathways. Furthermore, our data support both an intact protein core structure and carbohydrate side chains are important for the different protein-binding capacities of THP. Prospectively, parts of the whole THP molecule may be used for anti-TNF-α therapy in inflammatory diseases, autoantibody-depleting therapy in autoimmune disorders, and immune intensification in immunocompromised hosts. View Full-Text
Keywords: Tamm–Horsfall protein (THP); immunomodulation; renal tubular biomarker; polymorphonuclear leukocyte phagocytosis; protein-binding capacity Tamm–Horsfall protein (THP); immunomodulation; renal tubular biomarker; polymorphonuclear leukocyte phagocytosis; protein-binding capacity
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Wu, T.-H.; Li, K.-J.; Yu, C.-L.; Tsai, C.-Y. Tamm–Horsfall Protein is a Potent Immunomodulatory Molecule and a Disease Biomarker in the Urinary System. Molecules 2018, 23, 200.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top