Wednesday, December 11, 2019

Intestinal Cell Proliferation and Differentiation - myassignmenthelp

Question: Discuss about theIntestinal Cell Proliferation and Differentiationfor Tyrosine. Answer: Intestinal cell proliferation Several growth factors mediate the process of proliferation that triggers cells to enter cell cycle. Proliferation of the mucosal cells is needed to maintain the integrity of the gastrointestinal system. The EFGR gene sends instruction for production of the Epidermal growth factor receptor protein, which promotes cell proliferation. It is atransmembrane protein and is activated by specific ligand binding. Upon activation, EGFR undergoes dimerization, which stimulates tyrosine kinase activity. The tyrosine residues get autophosphorylated and activate downstream signaling of other pathways and promote proliferation. Receptor tyrosine kinase also influences the activity of insulin-like growth factor 1 and 2 encoded by the IGFR1 and IGFR2 genes respectively. Binding of ligand activates the receptor tyrosine kinase, autophosphoryaltion initiates intracellular signalling and activates the Akt and Ras MAPK pathway (Waseem et al. 2014). This increases proliferation and inhibits apoptosis. KL F4 or Krupple like factor 4 is a zinc-finger transcription factor, involved in regulation ofproliferation. KLF4 is expressed in non-dividing cells of the intestinal epithelium and maintains homeostasis in these cells.In the intestinal epithelium, it regulates Wnt signaling pathway of genes. Fibroblast growth factors (FGRFR2 and FGFR4) controls intestinal cell proliferation by binding to the receptor tyrosine kinase family. LGR5 promotes proliferation by acceleration of cell cycle. The main effect of high fat diet occurs in the colon, which leads to enhanced cell proliferation. Total lipids in feces are measured by a gravimetric method.Diet rich in saturated fats excerete more lipids. Proliferation of distal colon cell increases as fecal lipids increase (Sakar et al.2014). Intestinal cell differentiation A cell becomes more specialized through the process of differentiation. The EGFR, FGF-2, FGF-4, KLF4, HNF1a are responsible fot influencing the differentiation pathways of intestinal cells. Binding of specific ligands to the receptors encoded by these genes triggers the tyrosine kinsase activity. This activation occurs through dimerization of the receptors. Dimerization is followed by autophosphorylation and activation of downstream signaling pathways like Notch, BMP, Wnt/Wg, Hedgehog (Hh), mitogen-activated protein kinase (MAPK) and other pathways. Crypt structures and transient amplifying cells were rapidly lost due to block of the -catenin/Wnt signaling (Barker 2014). -Catenin is a cytoplasmic signal-transducer of the canonical Wnt pathway. In the absence of Wnt ligands, -catenin is phosphorylated and degraded. The degradation complex contains the tumor suppressor gene products conductin or axin, APC (adenomatous polyposis coli), casein kinase I (CKI) and glycogen synthase kinase 3. When the Wnt ligand binds to Frizzled transmembrane receptors, Disheveled cytoplasmic protein gets activated. It blocks the function of the degradation complex. -Catenin enters the nucleus and associates with LEF/TCF transcription factors. It induces transcriptional control of the Wnt target genes. Mutations which activate this pathway initiates colorectal cancer. The tumors are manifested by truncated mutation in axin and APC. Recently, several studies have reported that intestinal stem cells get inflamed and their differentiation is directly effected by prolonged consumption of saturated fat diet (Beyaz et al. 2016). References Barker, N., 2014. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration.Nature reviews. Molecular cell biology,15(1), p.19. Beyaz, S., Mana, M.D., Roper, J., Kedrin, D., Saadatpour, A., Hong, S.J., Bauer-Rowe, K.E., Xifaras, M.E., Akkad, A., Arias, E. and Pinello, L., 2016. High fat diet enhances stemness and tumorigenicity of intestinal progenitors.Nature,531(7592), p.53. Sakar, Y., Duca, F.A., Langelier, B., Devime, F., Blottiere, H., Delorme, C., Renault, P. and Covasa, M., 2014. Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation.International journal of obesity,38(11), p.1440. Waseem, T., Duxbury, M., Ashley, S.W. and Robinson, M.K., 2014. Ghrelin promotes intestinal epithelial cell proliferation through PI3K/Akt pathway and EGFR trans-activation both converging to ERK 1/2 phosphorylation.Peptides,52, pp.113-121.

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