Spatio-temporal expression profile of matrix metalloproteinase (Mmp) modulators Reck and Sparc during the rat ovarian dynamics

• Published in: Reproductive biology and endocrinology Vol. 16; no. 1; p. 116
• Main Authors: Levin, Gabriel, Coelho, Tatiane Maldonado, Nóbrega, Nathali Guimarães, Trombetta-Lima, Marina, Sogayar, Mari Cleide, Carreira, Ana Claudia Oliveira
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13-11-2018; BioMed Central; BMC
• Subjects: Animals; Basigin - genetics; Basigin - metabolism; Blood Proteins - genetics; Blood Proteins - metabolism; Cancer; Cattle; CD147 antigen; Corpus luteum; Estrous Cycle - genetics; Estrus cycle; Extracellular matrix; Female; Folliculogenesis; Gelatinase A; Gelatinase B; Gene expression; Gene Expression Profiling; Genetic aspects; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Homeostasis; Immunohistochemistry; Immunomodulation; Matrix metalloproteinase; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Menstrual cycle; Metalloproteinase; Mmps system; Osteonectin; Osteonectin - genetics; Osteonectin - metabolism; Ovarian cancer; Ovaries; Ovary - metabolism; Ovary remodeling; Ovulation; Ovulation - genetics; Physiological aspects; Proteases; Protein expression; Proteins; Rats, Sprague-Dawley; Reck; Rodents; Sexual Maturation - genetics; Sparc; Time Factors; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinases - genetics; Tissue Inhibitor of Metalloproteinases - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Brazil; Extracellular matrix; Sparc; Folliculogenesis; Reck; Mmps system; Ovary remodeling
• DOI: 10.1186/s12958-018-0422-2
• EISSN: 1477-7827

Matrix metalloproteinases (Mmps) and their tissue inhibitors (Timps) are widely recognized as crucial factors for extracellular matrix remodeling in the ovary and are involved in follicular growth, ovulation, luteinization, and luteolysis during the estrous cycle. Recently, several genes have been associated to the modulation of Mmps activity, including Basigin (Bsg), which induces the expression of Mmps in rat ovaries; Sparc, a TGF-β modulator that is related to increased expression of Mmps in cancer; and Reck, which is associated with Mmps inhibition. However, the expression pattern of Mmp modulators in ovary dynamics is still largely uncharacterized.
To characterize the expression pattern of Mmps network members in ovary dynamics, we analyzed the spatio-temporal expression pattern of Reck and Sparc, as well as of Mmp2, Mmp9 and Mmp14 proteins, by immunohistochemistry (IHC), in pre-pubertal rat ovaries obtained from an artificial cycle induced by eCG/hCG, in the different phases of the hormone-induced estrous cycle. We also determined the gene expression profiles of Mmps (2, 9, 13 14), Timps (1, 2, 3), Sparc, Bsg, and Reck to complement this panel.
IHC analysis revealed that Mmp protein expression peaks at the early stages of folliculogenesis and ovulation, decreases during ovulation-luteogenesis transition and luteogenesis, increasing again during corpus luteum maintenance and luteolysis. The protein expression patterns of these metalloproteinases and Sparc were inverse relative to the pattern displayed by Reck. We observed that the gene expression peaks of Mmps inhibitors Reck and Timp2 were closely paraleled by Mmp2 and Mmp9 suppression. The opposite was also true: increased Mmp2 and Mmp9 expression was concomitant to reduced Reck and Timp2 levels.
Therefore, our results generate a spatio-temporal expression profile panel of Mmps and their regulators, suggesting that Reck and Sparc seem to play a role during ovarian dynamics: Reck as a possible inhibitor and Sparc as an inducer of Mmps.