Central of Translation Medicine, Zibo Central Hospital, Shandong University, Zibo, China.
Department of Urology, Zibo Central Hospital, Shandong University, Zibo, China.
Arch Physiol Biochem. 2022 Aug;128(4):1050-1057. doi: 10.1080/13813455.2020.1749084. Epub 2020 Apr 7.
The membrane-bound transcription factor protease site 2 (MBTPS2) is an intramembranous metalloprotease involved in the regulation of ER stress response, however, whether it is associated with DN is unknown.
We report that MBTPS2 expression is upregulated in the renal cortex of diabetic mice induced by streptozotocin (STZ), a murine model of insulinopenic type 1 DN. Functionally, in vivo, MBTPS2 overexpression exacerbates and its knockdown attenuates albuminuria, which indicate a detrimental role of MBTPS2 played in albuminuria development in DN mice. We further show that MBTPS2 promotes ER stress and renal damage in DN mice, and that reducing ER stress via a chemical chaperone 4-phenylbutyric acid (4-PBA) markedly rescues MBTPS2-exacerbated renal damage and albuminuria severity.
Collectively, our study associates the function of MBTPS2 in DN albuminuria with ER stress regulation, thus underscoring the notorious role of maladaptive ER response in influencing DN albuminuria.
膜结合转录因子蛋白酶位点 2（MBTPS2）是一种跨膜金属蛋白酶，参与内质网应激反应的调节，但它是否与糖尿病肾病（DN）有关尚不清楚。
我们报告称，在链脲佐菌素（STZ）诱导的胰岛素缺乏型 1 型糖尿病肾病（DN）小鼠的肾脏皮质中，MBTPS2 的表达上调。在体内功能上，MBTPS2 的过表达加重而敲低则减轻蛋白尿，表明 MBTPS2 在 DN 小鼠蛋白尿发展中起有害作用。我们进一步表明，MBTPS2 促进了 DN 小鼠的内质网应激和肾脏损伤，而通过化学伴侣 4-苯丁酸（4-PBA）减轻内质网应激可显著挽救 MBTPS2 加重的肾脏损伤和蛋白尿严重程度。
总的来说，我们的研究将 MBTPS2 在 DN 白蛋白尿中的功能与内质网应激调节联系起来，从而强调了适应性内质网反应在影响 DN 白蛋白尿中的不良作用。
