Fibulin-5 plays 2 roles in preventing pelvic organ prolapse

Evidence is mounting that pelvic organ prolapse (POP) results from a disruption in the balance between the buildup and breakdown of the extracellular matrix in pelvic tissues. Operating on this premise, researchers found that a key protein, fibulin-5, prevents the development of POP in mice.

Researchers from the University of Texas Southwestern Medical Center in Dallas found that fibulin-5, an integrin-binding matricellular protein, works to prevent the development of POP in mice in 2 ways: It facilitates the assembly of normal elastic fibers that help keep pelvic organs where they should be and, in murine vaginal stromal cells, fibulin-5 inhibits upregulation of MMP-9, a protein that degrades the elastic fibers that hold pelvic organs in place.

Vaginal tissue samples from women with POP show increased levels of MMP-9. The data show that both abnormal elastic fibers and upregulation of MMP-9 are necessary for the development of POP in mice.

The author of an accompanying commentary notes that several questions remain. First, the means by which hormonal and aging mechanisms affect these pathways is not yet known. The researchers demonstrated that although levels of MMP-9 were significantly increased in women with POP compared with controls, the difference between postmenopausal women with POP versus controls was huge (23-fold), while the difference in premenopausal women with POP versus controls was small (3-fold), suggesting that hormones play a role in modulating the process.

Budatha M, Roshanravan S, Zheng Q, et al. Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest. 2011;121(5): 2048-2059.

Northington GM. Fibulin-5: two for the price of one maintaining pelvic support. J Clin Invest. 2011;121(5):1688-1691.