The two isoforms of matrix metalloproteinase- 2 have distinct renal spatial and temporal distributions in murine models of types 1 and 2 diabetes mellitus.
The two isoforms of matrix metalloproteinase- 2 have distinct renal spatial and temporal distributions in murine models of types 1 and 2 diabetes mellitus.
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DOI：
10.1186/s12882-018-1029-8
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发表时间：
2018-09-25
期刊：
影响因子：
2.3
通讯作者：
Song SH
中科院分区：
文献类型：
--
作者：
Kim IY;Kim SS;Lee HW;Bae SS;Ha HK;Jung ES;Lee MY;Han M;Rhee H;Seong EY;Lee DW;Lee SB;Lovett DH;Song SH
我们最近报道了两种不同的 MMP-2 亚型（全长和 N 末端截短的 FL-MMP-2、NTT-MMP-2）在小鼠模型和人类糖尿病肾脏中的肾小管表达增强。在本研究中，我们更详细地研究了 1 型和 2 型糖尿病小鼠模型中 MMP-2 同工型表达的时间和空间分布。糖尿病模型是链脲佐菌素 (STZ) 诱导的糖尿病（1 型糖尿病）和 db/db 小鼠（2 型糖尿病）。我们通过 qPCR 定量了 MMP-2 转录本的两种亚型的丰度。根据注射 STZ 后的时间以及随着 db/db 小鼠年龄的增加，半定量分析 MMP-2 两种亚型的空间分布。此外，还进行硝基酪氨酸免疫组织化学检查氧化应激与 MMP-2 亚型表达之间的潜在关联。 MMP-2 的两种亚型在 STZ 和 db/db 小鼠的整个肾脏中均上调。就 FL-MMP-2 而言，STZ 小鼠的 mRNA 水平在 12 周和 24 周时显着增加，而 db/db 小鼠的亚型表达仅在 16 周时显着增加。 STZ 和 db/db 小鼠的皮质和外髓质中的 FL-MMP-2 蛋白水平随着糖尿病持续时间的增加而增加。对于 NTT-MMP-2，STZ 小鼠 4 周龄和 db/db 小鼠 10 周龄时 mRNA 水平较早增加。 NTT-MMP-2 的表达也随着糖尿病持续时间的增加而增加，主要是在 STZ 和 db/db 小鼠的皮质中。从定量角度来看，这些结果分别与 NTT-MMP-2 情况下的 qPCR 结果一致（STZ 24 周，3.24±3.70 倍；16 周 db/db，4.49±0.55 倍）。此外，与髓质相比，硝基酪氨酸主要在皮质中表达，作为糖尿病持续时间的函数，类似于 NTT-MMP-2 表达。 MMP-2 的两种亚型在两种糖尿病小鼠模型中高度可诱导，并且随着时间的推移变得更加丰富。由于 MMP-2 的两种同工型的表达模式不同，因此每种同工型可能在糖尿病肾损伤的发展中具有不同的作用。
We recently reported on the enhanced tubular expression of two discrete isoforms of the MMP-2 (full length and N-terminal truncated, FL-MMP-2, NTT-MMP-2) in a murine model and human diabetic kidneys. In the present study, we examined in more detail the temporal and spatial distributions of MMP-2 isoform expression in murine models of Type 1 and Type 2 diabetes mellitus. Diabetic models were streptozotocin (STZ)-induced diabetes (Type 1 diabetes mellitus) and db/db mice (Type 2 diabetes mellitus). We quantified the abundance of two isoforms of MMP-2 transcripts by qPCR. A spatial distribution of two isoforms of MMP-2 was analyzed semi-quantitatively according to time after injection of STZ and with increasing age of db/db mice. Furthermore, immunohistochemistry for nitrotyrosine was performed to examine a potential association between oxidative stress and MMP-2 isoform expression. Both isoforms of MMP-2 were upregulated in whole kidneys from STZ and db/db mice. In the case of FL-MMP-2, mRNA levels significantly increased at 12 and 24 weeks in STZ mice, while the isoform expression was significantly increased only at 16 weeks, in the db/db mice. FL-MMP-2 protein levels increased in the cortices and outer medullae of both STZ and db/db mice as a function of the duration of diabetes. For NTT-MMP-2, mRNA levels increased earlier at 4 weeks in STZ mice and at 10 weeks of age in db/db mice. The expression of NTT-MMP-2 also increased, primarily in the cortices of STZ and db/db mice, as a function of the duration of diabetes. Quantitatively, these findings were consistent with the qPCR results in the case of NTT-MMP-2, respectively (STZ 24 weeks, 3.24 ± 3.70 fold; 16 weeks db/db, 4.49 ± 0.55 fold). In addition, nitrotyrosine was expressed primarily in cortex as compared to medulla as a function of the duration of diabetes similar to NTT-MMP-2 expression. Two isoforms of MMP-2 are highly inducible in two diabetic murine models and become more abundant as a function of time. As the expression patterns were not the same in the two isoforms of MMP-2, it is possible that each isoform has a discrete role in the development of diabetic renal injury.
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影响因子：
4
作者：
Lovett DH;Chu C;Wang G;Ratcliffe MB;Baker AJ
通讯作者：
Baker AJ
影响因子：
4.1
作者：
Xu X;Xiao L;Xiao P;Yang S;Chen G;Liu F;Kanwar YS;Sun L
通讯作者：
Sun L
影响因子：
3.7
作者：
Lovett DH;Mahimkar R;Raffai RL;Cape L;Maklashina E;Cecchini G;Karliner JS
通讯作者：
Karliner JS
基质金属蛋白酶-2的两个不同的同工型与人类延迟的肾移植功能有关。
影响因子：
3.7
作者：
Wanga S;Ceron CS;Delgado C;Joshi SK;Spaulding K;Walker JP;Song S;Olson JL;Lovett DH
通讯作者：
Lovett DH
影响因子：
3.7
作者：
Kim SS;Shin N;Bae SS;Lee MY;Rhee H;Kim IY;Seong EY;Lee DW;Lee SB;Kwak IS;Lovett DH;Song SH
通讯作者：
Song SH