INK-4a Downregulated in P53 and P21 Mutation Induce BAT and VSMCs Proliferation: Obesity and Hypertension
Abstract
Background: Epidemiology of obesity and hypertension are in high prevalence on low- and middle-neighborhood socioeconomic status (nSES) area. Later, the subjects become Diabetes and Chronic Kidney Diseases (CKDs) 1-5, and cancer due to p53, p21 and p16 mutation in AFB1 exposure population. Neglected p16/INK4a upregulated in early years which induce stunting, later induce proliferation of BAT (Uncoupling Protein UCPs132) or central Obesity, and vascular smooth muscle cells (VSMCs)/Hypertension.
Aims: p16 first upregulated in p21 and p53 mutation due to AFB1 exposure cause stunting, then when p16 downregulated in the older age induce cancer cells proliferation. This study recorded more the proliferation, reveal proliferation of BAT and VSMCs in healthy young age, in the downregulated p16 stage.
Method: Review article of Systematic Review and Meta-Analysis references of p16/INK-4a decreasing induced proliferation, also p16 Knock Out (KO) in p21/ p53 mutation population (AFB1 exposure).
Result: Mutation of p21/p53 in AFB1 exposure, induce p16/INK-4a downregulated in central Obese & VSMCs patients. Silencing/ downregulated p16/INK-4a induced proliferation, but still controversial with the upregulated in p53/p21 mutation (before).
Discussion: Proliferation of UCPs132 BAT cells, proliferation of SMCs, SGLT-2/GLP-1 therapy.
Conclusion: proliferation of BAT UCPs132 (central obesity) or VSMCs (hypertension) is due to downregulated p16 under p21/p53 mutation due to AFB1 exposure in low- and middle-nSES area population.
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Introduction
There are so many controversies in Obesity and Diabetes, especially in nature or nurture,1 geographical or eating habit,2 also in p53-p21-p16 upregulated or downregulated in this high prevalence area. p16 is a protein that slows cell division, by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the P16 gene, the name of p16 is derived from its molecular weight 16 kD, and the similar name INK4 refers to its role in inhibiting CKD4 (cyclin-dependent kinase) involved in regulation of the cell cycle, act as tumor suppressor cells and stunting. Down regulated of p16/INK-4a (by p53 mutation) in UCPs 132,3 VSMCs,4 and later proliferation of cancer cells in AFB1 exposure population.5 Uncoupling proteins are abundant in mitochondria of Brown Adipose Tissue (BAT) cells, function as thermogenesis metabolism, low of ATP synthesis, like the metabolism of hibernate bears.
The down regulation of p16 is controversial with upregulated p16Ink4, is as a suppressor protein that considered a tumor suppressor protein because both are high in p53 and p21 mutation in cancer patients and senescence.5,6 The Paradoxical downregulated7 of p16 mRNA with advancing age in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer,8 unlike healthy cells. P16 upregulated as a compensate of the failure of p53 and p21 tumor suppressor cells.6,7 The p16 pathway is a key regulator of the cell cycle, which controls the passage of cells from G, to S phase.
Conclusion
Proliferation of BAT UCP132 (obesity) or SMCs (hypertension) is due to downregulated p16 under p21/p53 mutation due to AFB1 exposure in low- and middle nSES area population with high childhood stunting (cell senescence) prevalence.