TIGAR deficiency sensitizes angiotensin-II-induced renal fibrosis and glomerular injury.
TIGAR deficiency sensitizes angiotensin-II-induced renal fibrosis and glomerular injury.
复制标题
DOI：
10.14814/phy2.15234
复制
发表时间：
2022-04
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
--
作者：
血管紧张素II （Ang‐II）是肾脏纤维化、炎症、肾小球损伤和慢性肾脏疾病进展的主要因素之一。新的证据表明，肾糖酵解在肾纤维化和损伤中起重要作用。TP53诱导的糖酵解和凋亡调节因子（TIGAR）已被证明可以调节糖酵解。在本研究中，我们研究了TIGAR在Ang‐II诱导的高血压期间肾糖酵解、纤维化和肾小球损伤中的作用。野生型（WT）和TIGAR敲除型（KO）小鼠通过微型泵注入Ang‐II(1µg/kg/min)，持续4周。WT和TIGAR - KO小鼠的平均动脉压相似，血浆肌酐水平也相应升高。在TIGAR - KO小鼠中，Ang‐II输注导致肾间质纤维化显著增加，肾系膜扩张和肾小球结构塌陷。与WT小鼠相比，这些与输注Ang - II后TIGAR KO小鼠缺氧诱导因子- 1 α、糖酵解酶和转化生长因子- 1的表达升高有关。偶联酶法显示，在输注Ang‐II后，WT和TIGAR - KO小鼠的PFK‐1活性相似地增加。我们目前的研究表明，TIGAR参与了Ang - II诱导的肾纤维化和肾小球损伤，尽管它对血压和肾功能的影响很小。敲除TIGAR可致敏Ang - II诱导的肾纤维化和损伤。这项研究为TIGAR在Ang‐II诱导高血压期间肾脏代谢和病理重塑中的作用提供了新的见解。敲除TIGAR可致敏小鼠肾脏中Ang II介导的HIF - 1α和TGF - β的表达。敲除TIGAR可增强Ang - II诱导的肾间质纤维化的增加，以及更多的肾系膜扩张和毛细血管塌陷。这项研究为TIGAR在Ang‐II诱导高血压期间肾脏代谢和病理重塑中的作用提供了新的见解。
Angiotensin II (Ang‐II) is one of the major contributors to the progression of renal fibrosis, inflammation, glomerular injury, and chronic kidney disease. Emerging evidence suggests that renal glycolysis plays an important role in renal fibrosis and injury. TP53‐induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glycolysis. In the present study, we investigated the role of TIGAR in renal glycolysis, fibrosis, and glomerular injury during Ang‐II‐induced hypertension. Wild‐type (WT) and TIGAR knockout (KO) mice were infused with Ang‐II (1 µg/kg/min) via mini‐pumps for 4 weeks. The mean arterial pressure was similar between the WT and TIGAR KO mice, associated with a comparable increase in plasma creatinine level. Ang‐II infusion resulted in a significant increase in renal interstitial fibrosis and more mesangial expansion and collapsed glomerular structure in the TIGAR KO mice. These were associated with elevated expression of hypoxia‐inducible factor‐1 alpha, glycolytic enzymes, and transforming growth factor beta 1 in the TIGAR KO mice after Ang‐II infusion when compared to that of the WT mice. The coupled‐enzyme method revealed that PFK‐1 activity was similarly increased in WT and TIGAR KO mice after Ang‐II infusion. Our present study suggests that TIGAR is involved in Ang‐II‐induced renal fibrosis and glomerular injury, although it has little effect on blood pressure and renal function. Knockout of TIGAR sensitizes Ang‐II‐induced renal fibrosis and injury. This study provides new insights into the role of TIGAR in renal metabolism and pathological remodeling during Ang‐II‐induced hypertension. Knockout of TIGAR sensitizes Ang II‐mediated HIF‐1α and TGF‐β expression in the mouse kidney. Knockout of TIGAR enhances Ang‐II‐induced increase in renal interstitial fibrosis as well as more mesangial expansion and collapsed capillaries. This study provides new insights into the role of TIGAR in renal metabolism and pathological remodeling during Ang‐II‐induced hypertension.