Semin Reprod Med 2010; 28(3): 180-203
DOI: 10.1055/s-0030-1251476
© Thieme Medical Publishers

Proinflammatory and Profibrotic Mediators: Principal Effectors of Leiomyoma Development as a Fibrotic Disorder

Nasser Chegini1
  • 1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida
Further Information

Publication History

Publication Date:
22 April 2010 (online)

ABSTRACT

Leiomyomas are believed to derive from the transformation of myometrial smooth muscle cells/connective tissue fibroblasts. Although the identity of the molecule(s) that initiate such cellular transformation and orchestrate subsequent growth is still unknown, conventional evidence indicates that ovarian steroids are essential for leiomyoma growth. Ovarian steroid action in their target cell/tissue is mediated in part through local expression of various growth factors, cytokines, and chemokines. These autocrine/paracrine molecules with proinflammatory and profibrotic activities serve as major contributing factors in regulating cellular transformation, cell growth and apoptosis, angiogenesis, cellular hypertrophy, and excess tissue turnover, events central to leiomyoma growth. This review addresses the key regulatory functions of proinflammatory and profibrotic mediators and their molecular mechanisms, downstream signaling that regulates cellular events that result in transformation, and commitments of specific cells into forming a cellular environment with a possible role in development and subsequent growth of leiomyomas.

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  • 260 Tili E, Croce C M, Michaille J J. miR-155: on the crosstalk between inflammation and cancer.  Int Rev Immunol. 2009;  28(5) 264-284
  • 261 Tili E, Michaille J J, Cimino A et al.. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock.  J Immunol. 2007;  179(8) 5082-5089
  • 262 Tili E, Michaille J J, Costinean S, Croce C M. MicroRNAs, the immune system and rheumatic disease.  Nat Clin Pract Rheumatol. 2008;  4(10) 534-541
  • 263 Chegini N, Zhao Y, Williams R S, Flanders K C. Human uterine tissue throughout the menstrual cycle expresses transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and TGF beta type II receptor messenger ribonucleic acid and protein and contains [125I]TGF beta 1-binding sites.  Endocrinology. 1994;  135(1) 439-449
  • 264 Chegini N, Ma C, Tang X M, Williams R S. Effects of GnRH analogues, ‘add-back’ steroid therapy, antiestrogen and antiprogestins on leiomyoma and myometrial smooth muscle cell growth and transforming growth factor-beta expression.  Mol Hum Reprod. 2002;  8(12) 1071-1078

Nasser CheginiPh.D. 

Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology

University of Florida, Gainesville, FL, 32610

Email: cheginin@ufl.edu

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