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journal article·2026-06-12Open access

BIN1 and ALDH1B1 Deficiency in Colonic Smooth Muscle Drives Mitochondrial Dysfunction and Fibrosis in Slow‐Transit Constipation

Jianbo Liu, Hao Zhang, Wenhao Qiao, Ran Liu, Jie Sun, Xiaopei Li, Qin Li, Dongbo Zhao, Dawei Chen, Jingxin Li, Shuxiao Dong

Advanced Science
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Abstract

ABSTRACT Slow‐transit constipation (STC) is a disabling motility disorder with unclear smooth‐muscle mechanisms. Through spatial proteomics of human colon and functional assays in primary human colonic smooth muscle cells (HCoSMCs), we identified Bridging Integrator 1 (BIN1) and Aldehyde Dehydrogenase 1B1 (ALDH1B1) as key regulators of intestinal motility. Both proteins were markedly reduced in smooth muscle from STC patients and localized to fibrotic areas. Lentiviral knockdown of BIN1 or ALDH1B1 impaired ATP‐evoked Ca 2 + responses and contraction, disrupted mitochondrial architecture, and increased reactive oxygen species. BIN1 deficiency activated mitochondrial apoptosis and extracellular matrix deposition, whereas ALDH1B1 loss induced mitophagy and NF‐κB–driven inflammation. Transcriptomic and histological analyses confirmed convergence on profibrotic pathways. Together, these findings reveal a smooth‐muscle‐centric mechanism underlying STC pathogenesis and nominate BIN1 and ALDH1B1 as promising therapeutic entry points to restore intestinal motility.
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Research context

Materials processing

OpenAlex topics: Gastrointestinal motility and disorders · Gastroesophageal reflux and treatments · Diet and metabolism studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gastrointestinal Surgery, Shandong Provincial Third Hospital Shandong University Jinan Shandong China

Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine Shandong University Jinan Shandong China

Department of Gastroenterology, Shandong Provincial Third Hospital Shandong University Jinan Shandong China

Department of Thoracic Surgery, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences Jinan Shandong China

Institute of Clinical Molecular Biology Kiel University Kiel Germany

School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University Nanjing China

Institute of Translational Medicine China Pharmaceutical University Nanjing China

Shandong Key Laboratory of Mental Disorders and Intelligent Control Jinan Shandong China

Funding

National Natural Science Foundation of China · Medical and Health Science and Technology Development Project of Shandong Province

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