Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Krakow, Poland.
Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Krakow, Poland.
Theriogenology. 2022 Jun;185:109-120. doi: 10.1016/j.theriogenology.2022.03.029. Epub 2022 Mar 31.
Matrix metalloproteinases (MMPs) are a family of enzymes that degrade extracellular matrix (ECM) molecules, playing a vital role in tissue remodeling under physiological and pathological conditions. Their expression and/or activity are regulated by specific tissue inhibitors of MMPs named TIMPs. Recently, an imbalance in the MMP/TIMP system has been found in human and bovine ovarian cysts, but its role in porcine cyst pathogenesis is unknown. This study examined mRNA expression, protein abundance and localization for selected members of the MMP/TIMP system in follicular cysts of sows. Based on histological analysis, we have assessed follicular (FC) and follicular lutein (FLC) cysts with preovulatory follicles (PF) used as a control. Regarding the pattern of MMP expression, increased MMP2, MMP7 and MMP9 mRNA levels were observed in FLC. Furthermore, both pro- and active forms of MMP-2 and MMP-9 proteins were more abundant in FLC. In FC, the abundance of latent and active forms of MMP-9 and the active form of MMP-2 were greater when compared with PF. In relation to TIMPs, TIMP-2 mRNA and protein expression were increased in FLC, whereas TIMP-3 was up-regulated in both FC and FLC only at the protein level. Using immunofluorescence, MMP-2, MMP-7, TIMP-2 and TIMP-3 were detected in granulosa and theca compartments of FC and within the entire luteinized wall of FLC. Notably, MMP-9 occurred weakly in the granulosa layer of FC, but abundantly in the theca compartment of FC and in the luteinized FLC. Taken together, our findings indicate altered expression of the MMP/TIMP system, suggestive of increased ECM degradation, in sow follicular cysts. These components may be involved in the pathogenesis of porcine ovarian cysts through the ECM remodeling.
基质金属蛋白酶(MMPs)是一类能够降解细胞外基质(ECM)分子的酶,在生理和病理条件下的组织重塑中发挥着至关重要的作用。它们的表达和/或活性受到特定的基质金属蛋白酶组织抑制剂(TIMPs)的调节。最近,在人类和牛的卵巢囊肿中发现 MMP/TIMP 系统失衡,但在猪的囊肿发病机制中其作用尚不清楚。本研究检测了 MMP/TIMP 系统中选定成员在母猪滤泡囊肿中的 mRNA 表达、蛋白丰度和定位。根据组织学分析,我们评估了卵泡(FC)和卵泡黄体(FLC)囊肿,以排卵前卵泡(PF)作为对照。关于 MMP 表达模式,FLC 中 MMP2、MMP7 和 MMP9 的 mRNA 水平升高。此外,MMP-2 和 MMP-9 的前体和活性形式的蛋白在 FLC 中更为丰富。在 FC 中,与 PF 相比,MMP-9 的潜伏和活性形式以及 MMP-2 的活性形式的丰度更大。关于 TIMPs,FLC 中 TIMP-2 的 mRNA 和蛋白表达增加,而 FC 和 FLC 中仅在蛋白水平上调了 TIMP-3。通过免疫荧光,在 FC 的颗粒层和膜层以及整个黄体化的 FLC 壁内检测到 MMP-2、MMP-7、TIMP-2 和 TIMP-3。值得注意的是,MMP-9 在 FC 的颗粒层中弱表达,但在 FC 的膜层和黄体化的 FLC 中丰富表达。综上所述,我们的研究结果表明母猪卵泡囊肿中 MMP/TIMP 系统的表达发生改变,提示 ECM 降解增加。这些成分可能通过 ECM 重塑参与猪卵巢囊肿的发病机制。