Horm Metab Res 2002; 34(5): 275-278
DOI: 10.1055/s-2002-32143
Short Communication
© Georg Thieme Verlag Stuttgart · New York

Reorganization of Thyrocyte Monolayers into Three-Dimensional Follicular Structures Correlates with Major Changes in Urokinase Production

B.  Degryse1
  • 1Laboratoire de Biochimie Médicale, Faculté de Médecine, Marseille, France
Further Information

Publication History

8 October 2001

5 February 2002

Publication Date:
10 June 2002 (online)

Introduction

The follicle represents the functional unit of the thyroid gland. It is composed of a single layer of polarized cells forming a spherical structure which encloses a lumen where the thyroid prohormone, thyroglobulin, is stored. This three-dimensional organization is essential for thyroid function - synthesis and secretion of thyroid hormones.

Folliculogenesis is a complex process, which is poorly understood. Possible mechanisms are cell migration and, to a lesser extent, cell proliferation [1]. TSH promotes follicle formation through generation of cAMP. Conversely, reconstruction of three-dimensional structures mimics some of the effects of TSH on thyroid cells [2]. Moreover, goitrogenesis, which is often observed in thyroid pathology and is accompanied by hyperplasia and hypertrophy, involves cell migration, cell proliferation, tissue remodeling, and angiogenesis.

Urokinase (uPA) is a serine protease that has been involved in a large number of physiological and pathological events such as fibrinolysis, wound healing, tissue involution, inflammation, angiogenesis, and cancer (reviewed in [3]). uPA is released by cells as an inactive single-chain precursor, pro-uPA, which can be activated by proteolytic cleavage of a single peptide bond into a double-chain HMW-uPA (High-Molecular Weight form). Further degradation leads to an active LMW-uPA (Low-Molecular Weight form). These molecules differ in their binding capacity to the uPA receptor (uPAR/CD87); pro-uPA and HMW-uPA can bind to uPAR, whereas LMW-uPA cannot. By activating plasminogen into plasmin, uPA can cause to the degradation of extracellular matrix (ECM) proteins that might facilitate cell migration through the ECM. But uPA function is not limited to the regulation of pericellular proteolysis; uPA regulates cell adhesion, migration, and proliferation. Indeed, uPA binding to its cellular receptor uPAR induces a migratory response and increases the affinity of uPAR for vitronectin, an ECM component, thus regulating cell migration and adhesion [3] [4].

Thyroid cells produce uPA; uPA expression is hormonally regulated [5] [6] [7]. Porcine thyroid cells embedded in collagen I reorganize into inside-out follicle-like structures with a small lumen. Addition of TSH leads to follicle-like structures with correct inside-in polarity and cells exhibit numerous microvilli at the apical pole facing a large lumenal compartment [8].

On the basis of the observations described above, reconstruction of three-dimensional follicular structures might affect uPA synthesis. In this study using porcine thyroid cells in culture, we show that formation of three-dimensional inside-out follicle-like structures can result in a great increase in urokinase production when compared to monolayers. Furthermore, difference in cell polarity, inside-in vs. inside-out follicle-like structures, quantitatively and qualitatively regulates uPA production.

References

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Bernard Degryse

Division of Vascular Biology/VB3 · Department of Cell Biology · The Scripps Research Institute

10550 North Torrey Pines Road · La Jolla, CA 92037 · USA ·

Phone: + 1 (858) 7847 153

Fax: + 1 (858) 7847 353

Email: degryse@scripps.edu

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