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Novel regulatory roles of small leucine-rich proteoglycans in remodeling of the uterine cervix in pregnancy
Matrix Biology ( IF 6.9 ) Pub Date : 2021-12-01 , DOI: 10.1016/j.matbio.2021.11.004
Mariano Colon-Caraballo 1 , Nicole Lee 2 , Shanmugasundaram Nallasamy 3 , Kristin Myers 2 , David Hudson 4 , Renato V Iozzo 5 , Mala Mahendroo 1
Affiliation  

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix.



中文翻译:

Novel regulatory roles of small leucine-rich proteoglycans in remodeling of the uterine cervix in pregnancy,富含亮氨酸的小蛋白多糖在妊娠期子宫颈重塑中的新调节作用,富含亮氨酸的小蛋白多糖在妊娠期子宫颈重塑中的新调节作用

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix.

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子宫颈经历了胶原蛋白和弹性纤维结构的快速而显着的变化,以实现其在怀孕期间的能力和分娩期间的顺应性的不同生理作用。了解胶原蛋白和弹性纤维的结构功能关系以维持细胞外基质 (ECM) 稳态需要了解非结构性 ECM 分子执行的机制。富含小亮氨酸的蛋白多糖 (SLRP) 通过影响胶原原纤维形成和调节酶和生长因子的生物活性,在生物学中发挥着关键作用。在当前的研究中,我们使用核心蛋白聚糖和/或双糖链聚糖基因作为 I 类 SLRP 代表的小鼠和 II 类 SLRP 代表的 lumican 基因的小鼠评估了小鼠宫颈中的胶原蛋白和弹性纤维结构-功能关系。我们在缺乏核心蛋白聚糖、双糖链蛋白聚糖或荧光蛋白聚糖的非妊娠小鼠中发现了胶原蛋白原纤维和弹性纤维组织的结构缺陷,并在怀孕期间发现了不同分辨率的缺陷。缺乏核心蛋白聚糖和双糖链蛋白聚糖的未怀孕小鼠的胶原蛋白和弹性纤维缺陷的严重程度更高,并且缺陷在整个怀孕期间都保持不变。双糖链蛋白聚糖单独缺失会降低未怀孕小鼠的组织延展性,而核心蛋白聚糖和双糖链蛋白聚糖的缺失则表现为妊娠晚期破裂拉伸减少。与野生型未怀孕和怀孕对照相比,I 类 SLRP 无效小鼠的胶原蛋白交联密度相似。与野生型对照相比,在突变小鼠中观察到更宽范围的胶原纤维直径以及平均纤维间距的增加。总的来说,这些发现揭示了 I 类和 II 类 SLRP 作为妊娠期宫颈 ECM 重塑的关键调节因子的功能冗余和等级作用。这些结果扩大了我们对 SLRP 在维持子宫颈 ECM 稳态中所起关键作用的理解。

,

子宫颈经历了胶原蛋白和弹性纤维结构的快速而显着的变化,以实现其在怀孕期间的能力和分娩期间的顺应性的不同生理作用。了解胶原蛋白和弹性纤维的结构功能关系以维持细胞外基质 (ECM) 稳态需要了解非结构性 ECM 分子执行的机制。富含小亮氨酸的蛋白多糖 (SLRP) 通过影响胶原原纤维形成和调节酶和生长因子的生物活性,在生物学中发挥着关键作用。在当前的研究中,我们使用核心蛋白聚糖和/或双糖链聚糖基因作为 I 类 SLRP 代表的小鼠和 II 类 SLRP 代表的 lumican 基因的小鼠评估了小鼠宫颈中的胶原蛋白和弹性纤维结构-功能关系。我们在缺乏核心蛋白聚糖、双糖链蛋白聚糖或荧光蛋白聚糖的非妊娠小鼠中发现了胶原蛋白原纤维和弹性纤维组织的结构缺陷,并在怀孕期间发现了不同分辨率的缺陷。缺乏核心蛋白聚糖和双糖链蛋白聚糖的未怀孕小鼠的胶原蛋白和弹性纤维缺陷的严重程度更高,并且缺陷在整个怀孕期间都保持不变。双糖链蛋白聚糖单独缺失会降低未怀孕小鼠的组织延展性,而核心蛋白聚糖和双糖链蛋白聚糖的缺失则表现为妊娠晚期破裂拉伸减少。与野生型未怀孕和怀孕对照相比,I 类 SLRP 无效小鼠的胶原蛋白交联密度相似。与野生型对照相比,在突变小鼠中观察到更宽范围的胶原纤维直径以及平均纤维间距的增加。总的来说,这些发现揭示了 I 类和 II 类 SLRP 作为妊娠期宫颈 ECM 重塑的关键调节因子的功能冗余和等级作用。这些结果扩大了我们对 SLRP 在维持子宫颈 ECM 稳态中所起关键作用的理解。

更新日期:2022-02-03
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