Keywords
1. IMP1
2. IGF2BP1
3. RNA binding protein
4. Colonic repair
5. Inflammatory bowel disease
Recent studies have delved into the intricacies of molecular biology, uncovering the vital role played by RNA binding proteins in a variety of biological processes, including development, disease, and cellular repair mechanisms. One protein that has grabbed the attention of researchers is IMP1 (also known as IGF2BP1), which has been found to be a critical regulator of intestinal development and cancer. A study published in EMBO Reports titled “Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1″ sheds light on the importance of this protein in colonic epithelial repair, proposing a compelling connection to inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.
EMBO Rep. 2021 Aug 4;22(8):e47074
The study, conducted by a team of researchers from various institutions including the University of Pennsylvania Perelman School of Medicine, the Children’s Hospital of Philadelphia, and the Lewis Katz School of Medicine at Temple University, investigated the role of IMP1 in the colonic epithelium, particularly its function in wound healing and autophagy processes. Autophagy, a cellular “housekeeping” mechanism that involves the degradation and recycling of cellular components, is known to play a significant role in maintaining cellular homeostasis and responding to cellular damage.
Using both in vitro and in vivo models, the researchers demonstrated that deletion of the Imp1 gene in intestinal epithelial cells (IECs) led to impaired wound healing and defective autophagy. Through in silico analysis, they identified that IMP1 can bind to and regulate the stability and translation of mRNAs coding for essential autophagy-related proteins like MAP1LC3B, ATG3, ATG5, and Atg7, suggesting a posttranscriptional regulatory role for IMP1 in autophagy.
Considering that impaired autophagy has been associated with increased susceptibility to IBD, these findings underscore the potential consequences of dysfunctional IMP1 in the pathogenesis of such diseases. Prior research has identified autophagy-related genes, including ATG16L1 and NOD2, as risk factors for Crohn’s disease, affirming the connection between autophagy dysregulation and intestinal inflammation. The Imp1 knockout mice used in the study (Imp1 ΔIEC) exhibited increased severity of colonic injury, substantiating the regulatory influence of IMP1 on autophagy and its overarching impact on intestinal health.
In light of this study and past research, it becomes evident that a better understanding of the molecular mechanisms driving colonic repair is pivotal. The therapeutic targeting of IMP1 could offer a novel avenue for managing conditions like IBD where healing the epithelial barrier is crucial. Moreover, it opens doors for further investigation into how IMP1 might be manipulated to enhance repair mechanisms in the colonic epithelium.
The study not only contributes to our comprehension of IBD pathogenesis but also highlights the importance of maintaining a balanced autophagic process for intestinal health. Strategies aimed at modulating IMP1 levels or function could potentially mitigate the symptoms or progress of IBD by augmenting the cell’s ability to repair itself and cope with inflammatory insults.
This body of research further indicates that RNA binding proteins such as IMP1 are more than mere participants in posttranscriptional gene regulation. They are, in fact, key players in the maintenance of intestinal integrity and the human body’s response to gastrointestinal diseases. As the global incidence of IBD continues to rise, unveiling the molecular interactions and pathways influenced by proteins like IMP1 will be invaluable in the development of targeted treatments and diagnostics.
References
1. Chatterji, P., Williams, P. A., Whelan, K. A. et al. (2021). Posttranscriptional regulation of colonic epithelial repair by RNA binding protein IMP1/IGF2BP1. EMBO Rep, 22(8):e47074. doi: 10.15252/embr.201847074.
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