2. Academic Validation
  3. S-adenosyl-L-methionine supplementation alleviates the destructed intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency

S-adenosyl-L-methionine supplementation alleviates the destructed intestinal epithelium and inflammatory infiltration caused by Mat2a deficiency

  • Development. 2023 Mar 28;dev.201135. doi: 10.1242/dev.201135.
Miao-Lin Li 1,  Si-Yi Cao 1,  Jia Qu 1,  Lei Zhang 1,  Qiang Gao 2,  Xu Wang 1,  Miao Yin 1,  Ying Liu 3,  Ming-Zhu Lei 1,  Qun-Ying Lei 1
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, Shanghai Key Laboratory of Radiation Oncology, the Shanghai Key Laboratory of Medical Epigenetics, State Key Laboratory of Medical Neurobiology, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
  • 2 Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, 180 Fenglin Road, Shanghai 200032, China.
  • 3 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
PMID: 36975381 DOI: 10.1242/dev.201135
Abstract

Methionine is important for intestinal development and homeostasis in various organisms. However, the underlying mechanisms are poorly understood. Here, we define that Mat2a is essential for intestinal development and metabolite S-adenosyl-L-methionine (SAM) plays an important role in intestinal homeostasis. Intestinal epithelial cells (IECs)-specific knockout of Mat2a exhibits impaired intestinal development and neonatal lethality. Mat2a deletion in the adult intestine reduces cell proliferation and triggers IECs Apoptosis, leading to severe intestinal epithelial atrophy and intestinal inflammation. Mechanistically, we reveal that SAM maintains the integrity of differentiated epithelium and protects IECs from Apoptosis by suppressing the expression of Caspase-8/3 and their activation. SAM supplementation improves the defective intestinal epithelium and reduces inflammatory infiltration sequentially. In conclusion, our study demonstrates that methionine metabolism and its intermediate metabolite SAM play essential roles in mice intestinal development and homeostasis.

Keywords

Mat2a; Intestinal development; Intestinal homeostasis; Intestinal inflammation; SAM.

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