Lenarczyk Marek, Pressly Jeffrey D, Arnett Joanna, Regner Kevin R, Park Frank
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences Center, 881 Madison Ave., Rm. 442, Memphis, TN, 38163, USA.
J Mol Histol. 2015 Apr;46(2):123-36. doi: 10.1007/s10735-014-9605-0. Epub 2014 Dec 23.
Activators of G-protein Signaling (AGS) are a family of accessory proteins that were discovered as modulators of heterotrimeric G-protein subunits. The primary aim of the present study was to localize Group I and II AGS proteins and determine the renal expression profile using immunohistochemistry and quantitative RT-PCR, respectively, during normal and injured states of the kidney. Group I AGS1 was found to be predominantly localized to the proximal tubule, Group II AGS3 and AGS5 were exclusively localized to the distal tubular segments, and Group II AGS6 was ubiquitously expressed in every nephron segment of the rodent kidney. In rat kidneys following ischemia-reperfusion injury (IRI), Group I AGS1 mRNA was dramatically increased after 24 h by fivefold (P < 0.05), whereas Group II AGS3 and AGS4 mRNA was significantly decreased at the same time point (P < 0.05). No significant change in the transcript levels were detected at other time points for any of the AGS genes between control and IRI groups. In polycystic diseased kidneys, mRNA levels for AGS3, AGS4 and AGS6 was significantly increased (P < 0.05) by 75-80 % in PCK rat kidneys. The identification of Group I and II AGS mRNA and protein in the kidney may provide insight into the potential mechanism of action during normal and varying states of renal disease or injury.
G蛋白信号激活剂(AGS)是一类辅助蛋白家族,最初作为异三聚体G蛋白亚基的调节剂被发现。本研究的主要目的是分别使用免疫组织化学和定量逆转录聚合酶链反应,在肾脏的正常和损伤状态下,定位I组和II组AGS蛋白并确定其在肾脏中的表达谱。发现I组AGS1主要定位于近端小管,II组AGS3和AGS5仅定位于远端小管节段,而II组AGS6在啮齿动物肾脏的每个肾单位节段中均有广泛表达。在大鼠肾脏缺血再灌注损伤(IRI)后,I组AGS1 mRNA在24小时后显著增加了五倍(P < 0.05),而II组AGS3和AGS4 mRNA在同一时间点显著降低(P < 0.05)。在对照和IRI组之间的任何其他时间点,未检测到任何AGS基因的转录水平有显著变化。在多囊肾病的肾脏中,PCK大鼠肾脏中AGS3、AGS4和AGS6的mRNA水平显著增加(P < 0.05),增幅为75 - 80%。在肾脏中鉴定I组和II组AGS mRNA和蛋白可能有助于深入了解肾脏疾病或损伤的正常和不同状态下的潜在作用机制。