2. Academic Validation
  3. Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2

Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2

  • Elife. 2023 Jan 16;12:e81438. doi: 10.7554/eLife.81438.
Xiaoliang Liu # 1,  Ting Yu # 2,  Xiaoqin Tan 1,  Daqing Jin 3,  Wenmin Yang 1,  Jiangping Zhang 1,  Lu Dai 1,  Zhongwei He 1,  Dongliang Li 3,  Yunfeng Zhang 1,  Shuyi Liao 1,  Jinghong Zhao 1,  Tao P Zhong 3,  Chi Liu 1
Affiliations

Affiliations

  • 1 Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 2 Department of Respiratory Medicine, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 3 Shanghai Key Laboratory of Regulatory Biology, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, School of Life Sciences, Shanghai, China.
  • # Contributed equally.
PMID: 36645741 DOI: 10.7554/eLife.81438
Abstract

In organ regeneration, progenitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation, and differentiation. However, the types of cells that form the native microenvironment for renal progenitor cells (RPCs) have not been clarified. Here, single-cell sequencing of zebrafish kidney reveals fabp10a as a principal marker of renal interstitial cells (RICs), which can be specifically labeled by GFP under the control of fabp10a promoter in the fabp10a:GFP transgenic zebrafish. During nephron regeneration, the formation of nephrons is supported by RICs that form a network to wrap the RPC aggregates. RICs that are in close contact with RPC aggregates express cyclooxygenase 2 (Cox2) and secrete prostaglandin E2 (PGE2). Inhibiting PGE2 production prevents nephrogenesis by reducing the proliferation of RPCs. PGE2 cooperates with Wnt4a to promote nephron maturation by regulating β-catenin stability of RPC aggregates. Overall, these findings indicate that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.

Keywords

PGE2; developmental biology; kidney; regeneration; renal interstitial cells; zebrafish.

Figures
Products