Biphasic dysregulation of non-muscle myosin IIA drives the AKI-to-CKD transition via an ALDH1A1–retinoic acid–HBEGF/EGFR signaling axis in tubular cells
4 affiliations
- 1Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, The Third Affiliated Hospital of Anhui Medical University, Hefei 230032, China
- 2Department of Pediatric, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 211000, China
- 3Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China
- 4Department of Pediatrics, Yancheng City No.1 People's Hospital, Yancheng 224000, China
Abstract
The decision between successful repair and pathological fibrosis following kidney injury remains a pivotal yet poorly understood process. Here, we identify non-muscle myosin IIA (NM IIA) as a master regulator of renal tubular fate whose biphasic dysregulation dictates the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Using integrated single-cell transcriptomics and multi-model validation, we define this dysregulation as stage-dependent alterations in NM IIA expression and subcellular localization: it is downregulated in AKI, impairing regenerative repair, but pathologically overexpressed and aberrantly localized to the nucleus in CKD, where it drives maladaptive fibrosis. Mechanistically, upon nuclear translocation in tubular epithelial cells, NM IIA directly transactivates Aldh1a1, thereby enhancing local retinoic acid (RA) biosynthesis. This RA signal subsequently propagates through HBEGF/EGFR signaling to influence repair outcomes. Collectively, our work delineates an NM IIA/ALDH1A1–RA–HBEGF/EGFR axis, revealing how NM IIA, beyond its cytoskeletal function, acts as a transcriptional regulator that integrates mechanical and metabolic cues in the kidney. These findings establish a mechanistic framework for the AKI-to-CKD transition and highlight potential stage-specific therapeutic targets.
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BibTeX
@article{he2026biphasic,
title = {{Biphasic dysregulation of non-muscle myosin IIA drives the AKI-to-CKD transition via an ALDH1A1–retinoic acid–HBEGF/EGFR signaling axis in tubular cells}},
author = {Ruobing He and Yingying Zhao and Shumin Li and Jun Qin and Xiaoming Meng and Xiaowen Yu},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jul,
doi = {10.1016/j.apsb.2026.07.005},
url = {https://europepmc.org/article/PMC/PMC13729534},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Biphasic dysregulation of non-muscle myosin IIA drives the AKI-to-CKD transition via an ALDH1A1–retinoic acid–HBEGF/EGFR signaling axis in tubular cells
AU - Ruobing He
AU - Yingying Zhao
AU - Shumin Li
AU - Jun Qin
AU - Xiaoming Meng
AU - Xiaowen Yu
PY - 2026
DA - 2026/07/08
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.07.005
UR - https://europepmc.org/article/PMC/PMC13729534
AB - The decision between successful repair and pathological fibrosis following kidney injury remains a pivotal yet poorly understood process. Here, we identify non-muscle myosin IIA (NM IIA) as a master regulator of renal tubular fate whose biphasic dysregulation dictates the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Using integrated single-cell transcriptomics and multi-model validation, we define this dysregulation as stage-dependent alterations in NM IIA expression and subcellular localization: it is downregulated in AKI, impairing regenerative repair, but pathologically overexpressed and aberrantly localized to the nucleus in CKD, where it drives maladaptive fibrosis. Mechanistically, upon nuclear translocation in tubular epithelial cells, NM IIA directly transactivates Aldh1a1, thereby enhancing local retinoic acid (RA) biosynthesis. This RA signal subsequently propagates through HBEGF/EGFR signaling to influence repair outcomes. Collectively, our work delineates an NM IIA/ALDH1A1–RA–HBEGF/EGFR axis, revealing how NM IIA, beyond its cytoskeletal function, acts as a transcriptional regulator that integrates mechanical and metabolic cues in the kidney. These findings establish a mechanistic framework for the AKI-to-CKD transition and highlight potential stage-specific therapeutic targets.
SN - 2211-3835
SN - 2211-3843
ER -