Abhilash Lankalapalli

Introduction

Fibroblast Growth Factor 10 (FGF10) is a paracrine signaling growth factor essential for lung development and organogenesis. FGF10 consists of two chains: Chain A (145 amino acids) and Chain B (225 amino acids), which work together to provide signals for epithelial cells in the lungs to regenerate. Researchers have successfully built tracheas and lungs from the ground up, demonstrating FGF10’s critical role in aiding cellular differentiation and synthesizing tissue. This study explores the intricate structure and function of FGF10 and its role in forming healthy lung tissues.

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Research Goal
To understand the structural and functional roles of Fibroblast Growth Factor 10 in lung regeneration.

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Methods

FGF10’s Pathway:

Once released from the cell, FGF10 binds to an FGFR receptor made up of three subdomains (D1, D2, and D3) and a transmembrane domain.
Binding causes dimerization of the receptor, stabilizing the protein and activating intracellular pathways.
Tyrosine kinases are activated, phosphorylating downstream molecules, including GRB and SOS proteins, which activate RAF and MAPK signaling pathways.
These pathways ultimately activate transcription factors, leading to cellular specialization and the regeneration of damaged or dead lung cells.
Binding Sites and Structures:

The unbound binding site 15P uses polyethylene glycol to improve stability and solubility. This enhances chain interaction and structure.
Buried residues store information crucial for catalytic activity and protein-protein interactions, while CIS peptide bonds maintain FGF10’s fold and structural integrity.
FGF10 regulates AT1 and AT2 cells for cellular differentiation. AT1 cells are critical for forming lung tissues, while AT2 cells specialize into AT1 during the regeneration process.
Signaling Pathway:

FGF10 uses secondary messages to relay genetic material to AT1 and AT2 cells, ensuring transcription and tissue formation.

Figures and Results
 

Figure 1: Unbound Binding Site 15P

Shows the interaction between chains to improve solubility and form stronger bonds.
Figure 2: Buried Residues

Highlights catalytic activity and protein-protein interactions essential for FGF10’s function.
Figure 3: CIS Peptide Bonds

Demonstrates structural integrity critical for FGF10’s unique folding and function.
Figure 4: FGF10 Signaling Pathway

Explains the transcription process and differentiation of AT1 and AT2 cells.

Conclusion
 

FGF10 plays a pivotal role in lung regeneration by regulating transcriptional processes, cellular differentiation, and structural integrity.

Binding Sites: The unbound binding site strengthens interactions, while CIS peptide bonds ensure stability, preventing denaturation.
Cellular Differentiation: AT2 cells differentiate into AT1 cells under FGF10’s influence, promoting tissue regeneration.
Gene Regulation: FGF10 transmits genetic information to epithelial cells, initiating mitosis and forming lung tissues.
This intricate structure and function make FGF10 vital for regenerating damaged lungs and enhancing the therapeutic potential of regenerative medicine.

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Acknowledgments

Special thanks to Darrell Kotton, Thomas H. Peterson, Ye-Rang Yun, and colleagues for their insights and mentorship. Additional thanks to Delegates Beyond Borders and my advisor Mohit Nadkarni for their guidance.

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References

Poem, T. H., Cohn, E. A., & Niklasson, L. E. (2011). Strategies for lung regeneration. Materials Today.
Watson, J., & Francavilla, C. (2022). Review of Regulation of FGF10 in signaling in development and disease. Frontiers.
Yun, Y.-R., Woo, J. E., Jeon, E., Lee, S., Kang, W. H., Jung, J., & Kim, K. (2020). Role of AT1 and AT2 cells in regenerative medicine. Nature Reviews.