Deletion of the RNLS Gene using CRISPR/Cas9 as Pancreatic Cell β Protection against Autoimmune and ER Stress for Type 1 Diabetes Mellitus

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease in children which is usually caused by autoimmunity that damages pancreatic a and b cells which have functions as blood glucose regulators. Some studies stated that Renalase (RNLS) gene deletion will protect these b cells from autoimmune reactions and Endoplasmic Reticulum (ER) stress. RNLS deletion by genome editing Clustered Regular interspersed Short Palindromic Repeats-CRISPR-related (CRISPR/Cas9) is believed to have the potential to be a therapy for T1DM Patients. AIM: This research was conducted to know the potential of RNLS deletion using the CRISPR/Cas9 as an effective therapy and whether it has a permanent effect on T1DM patients. METHODS: The method applied in this research summarized articles by analyzing the titles and abstracts of various predetermined keywords. In this case, the author chose a full-text article published within the past 10 years by prioritizing searches in the last 5 years through PubMed, Google Scholar, Science Direct, Cochrane, American Diabetes Association, and official guidelines from IDAI. RESULTS: RNLS deletion using CRISPR/Cas9 in mice weakened the response of polyclonal -cell-reactive CD8+ T cells and disrupted the immune recognition to cells so that autoimmune killing did occur. In addition, such deletion prevents RNLS ER stress by increasing the threshold, triggering the unfolded protein response so that ER stress is difficult to occur. RNLS mutations in b cells also increase b cell survivability to oxidative stress. CONCLUSION: b cells RNLS deletion by genome editing CRISPR/Cas9 is effective in protecting b cells from autoimmune reactions and RE stress. However, further research is needed to determine the side effects and safety of its use.

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B cells in type 1 diabetes mellitus and diabetic kidney disease

Nature Reviews Nephrology ◽

10.1038/nrneph.2017.138 ◽

2017 ◽

Vol 13 (11) ◽

pp. 712-720 ◽

Cited By ~ 17

Author(s):

Mia J. Smith ◽

Kimber M. Simmons ◽

John C. Cambier

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

B Cells ◽

Kidney Disease ◽

Type 1 Diabetes Mellitus ◽

Diabetic Kidney Disease ◽

Diabetic Kidney

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Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes

Antioxidants ◽

10.3390/antiox10050752 ◽

2021 ◽

Vol 10 (5) ◽

pp. 752

Author(s):

Aikaterini Kountouri ◽

Emmanouil Korakas ◽

Ignatios Ikonomidis ◽

Athanasios Raptis ◽

Nikolaos Tentolouris ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

B Cells ◽

Type 1 Diabetes Mellitus ◽

Pathophysiological Mechanism ◽

Necrosis Factor Alpha ◽

Angiotensin Converting Enzyme 2 ◽

Life Threatening

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a “cytokine storm”. Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.

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