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Thrombospondin-1 and Thrombospondin-2 mRNA and TSP-1 and TSP-2 Protein Expression in Uterine Fibroids and Correlation to the Genes COL1A1 and COL3A1 and to the Collagen Cross-link Hydroxyproline

Duke University, Department of Obstetrics and Gynecology, Durham, North Carolina

Liping Feng, MD

Duke University, Department of Obstetrics and Gynecology, Durham, North Carolina

Bryan Yonish, BA

Duke University, Department of Obstetrics and Gynecology, Durham, North Carolina

William Catherino, MD, PhD

Uniformed Services University, Department of Obstetrics and Gynecology, Bethesda, Maryland

Sin-Ho Jung, PhD

Duke University, Department of Biostatistics and Bioinformatics, Durham, North Carolina

Phyllis C. Leppert, MD, PhD

Duke University, Department of Obstetrics and Gynecology, Durham, North Carolina, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, phyllis.leppert@ duke.edu

Uterine fibroids are composed of altered collagen fibrils and represent an arrested response to injury-initiating fibrosis. In many tissues, TSP-1 is secreted by adult macrophages and monocytes upon wounding and is involved in the activation of transforming growth factor β. In the absence of TSP-1, the orchestrated process of wound healing is impaired. The authors obtained tissue from the edge and center of fibroids at the time of hysterectomy and compared them with adjacent myometrium. The pattern of TSP-1 and TSP-2 expression was correlated to that of COL1A1 and COL3A1. Collagen and hydroxyproline were increased in fibroids. Thrombospondin-1 was consistently underexpressed in both the edge and center of the fibroids, while COL1A1 and COL3A1 were consistently overexpressed. However, TSP-2 was inconsistently expressed. These findings lead to the conclusion that the underexpression of TSP-1 may contribute to the overall development of uterine fibroids.

Key Words: Uterine fibroids • leiomyomata • thrombospondins • collagen • fibroisis.

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