STM: Biological clock disorders? Research reveals new mechanisms of pancreatitis-circadian clock pathology and transformation

Evolutionary adaptation determines that most physiological processes in mammals follow cyclical peri-temporal fluctuations, and the molecular basis for their production is the endogenous circadian clock, which allows the body to predict changes in the external environment and synchronize changes in the internal environment

On September 28, 2022, Jiang Weiliang and Wan Rong's research group of the Digestive Center of the First People's Hospital Affiliated to Shanghai Jiao Tong University/Shanghai Key Laboratory of Pancreatic Diseases and the Erquan Zhang Group of the Beijing Institute of Life Sciences/Institute of Interdisciplinary Biomedical Sciences of Tsinghua University published an article entitled The pancreatic clock is a key determinant of pancreatic in Science Translational Medicine fibrosis progression and exocrine dysfunction, revealing the role

The study revolves around three key questions: First, does circadian disruption exist as a precursor or maintaining/driving factor in the onset of CP? How does the circadian clock regulate pancreatic exocrine and which elements play a leading role in complex timing systems? Can we target the circadian clock to predict or treat CP? The researchers first identified a significant disturbance of the circadian clock core transcription-translational feedback loop (TTFL) in pancreatic fibrotic tissues through clinical samples, with decreased expression of some components, weakened rhythm and amplitude

Animal experiments showed that both by interfering with the feeding patterns of mice or knocking out the core bell gene Bmal1 significantly aggravated pancreatic tissue damage and fibrosis, especially in the Bmal1-deficient mouse model, which showed a manifestation

Figure 1 Two independent animal models of chronic pancreatitis show the effect

On the other hand, researchers explore from the beginning the causes of disorders in the

Since Konopka and Benzer first discovered the first clock gene period mutation in fruit flies in the 1970s, theoretical research on biological clocks has gradually been systematically enriched and derived from a special "Chronobiology", and the Lasker Prize and Nobel Prize have also been awarded to outstanding workers in this field

Figure 2 Physiological/pathological patterns of pancreatic circadian clock regulation

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The first (and co-communicative) author of this paper, Dr.

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