1. Academic Validation
  2. Reduction of anaerobic glycolysis contributes to angiotensin II-induced podocyte injury with foot process effacement

Reduction of anaerobic glycolysis contributes to angiotensin II-induced podocyte injury with foot process effacement

  • Kidney Int. 2023 Jan 31;S0085-2538(23)00052-2. doi: 10.1016/j.kint.2023.01.007.
Zhaowei Chen 1 Zijing Zhu 1 Wei Liang 1 Zilv Luo 1 Jijia Hu 1 Jun Feng 1 Zongwei Zhang 1 Qiang Luo 1 Hongxia Yang 1 Guohua Ding 2
Affiliations

Affiliations

  • 1 Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China; Nephrology and Urology Research Institute of Wuhan University, Wuhan, China.
  • 2 Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China; Nephrology and Urology Research Institute of Wuhan University, Wuhan, China. Electronic address: ghxding@whu.edu.cn.
Abstract

Activation of the renin-angiotensin system is associated with podocyte injury and has been well demonstrated as a pivotal factor in the progression of chronic kidney disease. Podocyte energy metabolism is crucial for maintaining their physiological functions. However, whether renin-angiotensin system activation promotes chronic kidney disease progression by disturbing the energy metabolism of podocytes has not been elucidated. Angiotensin II, the main active molecule of the renin-angiotensin system, plays a crucial role in chronic kidney disease initiation and progression, but its impact on podocyte metabolism remains unclear. Here, we demonstrate a rapid decrease in the expression of Pyruvate Kinase M2, a key glycolytic Enzyme, and reduced glycolytic flux in podocytes exposed to angiotensin II in vivo and in vitro. Podocyte-specific deletion of Pyruvate Kinase M2 in mice aggravated angiotensin II-induced glomerular and podocyte injury with foot process effacement and proteinuria. The inhibition of glycolysis was accompanied by adenosine triphosphate deficiency, cytoskeletal remodeling and podocyte Apoptosis. Mechanistically, we found that angiotensin II-induced glycolysis impairment contributed to an insufficient energy supply to the foot process, leading to podocyte injury. Additionally, Pyruvate Kinase M2 expression was found to be reduced in podocytes from kidney biopsies of patients with hypertensive nephropathy and diabetic kidney disease. Thus, our findings suggest that glycolysis activation is a potential therapeutic strategy for podocyte injury.

Keywords

PKM2; angiotensin Ⅱ; glycolysis; podocyte injury.

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