The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

Thongsroy, Jirapan; Mutirangura, Apiwat

doi:10.1038/s41598-023-46431-2

Cited by 2 publications

(1 citation statement)

References 101 publications

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“…The role of Box A of HMGB1 in enhancing stem cell properties of human mesenchymal cells (13) was published by our group. Recently, we also reported that decreased youth-DNA-gap numbers were observed in patients with type 2 DM and associated with increased HbA1c levels (14). The DNA gap complex is composed of Box A of high mobility group Box 1 protein (Box A), which produces a DNA gap, Sirtuin 1 (SIRT1), which deacetylates histones, and Argonaute RISC component 4 (AGO4), which methylates DNA (15,16).…”

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confidence: 99%

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats

KHUMSRI,

PAYUHAKRIT,

KONGKAEW

et al. 2024

In Vivo

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Background/Aim: Disability and mortality rates for renal failure are still increasing. DNA damage and oxidative stress intoxication from body metabolism, high blood glucose, or the environment cause significant kidney damage. Recently, we reported that Box A of HMGB1 (Box A) acts as molecular scissors, producing DNA gaps that prevent DNA damage in kidney cell lines and ultimately reverse aging phenotypes in aging rat models. The present study aimed to demonstrate the potency of Box A in preventing D-galactose (D-gal)-induced kidney injury. Materials and Methods: A Box A expression plasmid was constructed and administered to a rat model. D-gal was injected subcutaneously for eight weeks. Serum was collected to study renal function, and white blood cells were collected for DNA gap measurement. Kidney tissue was also collected for γ-H2AX and NF-ĸB immunostaining; Senescence-associated (SA)-beta-gal staining; and analysis of the mRNA expression of p16 INK4A , TNF-α, and IL-6. Moreover, histopathology analysis was performed using hematoxylin & eosin and Masson trichome staining. Results: Pretreatment with Box A administration prevented the reduction of DNA gaps and the consequences of the DNA damage response, which include elevated serum creatinine; high serum BUN; an increased positive SA-beta-gal staining area; overexpression of p16 INK4A , NF-ĸB and senescenceassociated secretory phenotype molecules, including IL-6, TNF-α; and histological alterations, including tubular dilation and collagen accumulation. Conclusion: Box A effectively prevents DNA gap reduction and all D-gal-induced kidney pathological changes at the molecular, histological, and physiological levels. Therefore, Box A administration is a promising novel therapeutic strategy to prevent DNAdamaging agent-induced kidney failure.DNA damage and the associated DNA damage response (DDR) have been identified as common causes of kidney injury. Chemicals, ischemia-reperfusion injury, or sepsis can cause DNA damage with increased apoptosis of renal tubular epithelial cells, interstitial fibrosis, and ultimately chronic kidney disease (CKD) (1). Diabetes is a critical and commonly leading cause of CKD that accounts for nearly 50% of the 1170

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confidence: 99%

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats

KHUMSRI,

PAYUHAKRIT,

KONGKAEW

et al. 2024

In Vivo

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The role of Box A of HMGB1 in producing γH2AX-associated DNA breaks in lung cancer

Settayanon,

Chanvorachote,

Mutirangura

2024

Preprint

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An ideal chemotherapeutic agent damages DNA specifically in cancer cells without harming normal cells. Recently, we used a Box A of HMGB1 plasmid as a molecular scissor to produce a DNA gap protected by SIRT1. The DNA gap relieves DNA tension and increases DNA strength. Since the level of SIRT1 in many types of cancers is lower than that in normal cells, the outcome of DNA gaps produced by Box A may be different in cancer cells. We demonstrated the role of γH2AX-associated DNA double-strand breaks (DSBs) produced by Box A in lung cancer cells lacking SIRT1. We transfected Box A plasmid into lung cancer cell lines to overexpress Box A and evaluated the expression levels of DNA damage response (DDR) signaling cascade markers. Then, we demonstrated the effect of Box A-induced DSBs on lung cancer cell proliferation. Box A overexpression increased the levels of DDR signaling proteins, including γH2AX, ATM, ATR, and p53. It may also inhibit cancer cell growth and promote cancer cells death by apoptosis. Thus, Box A of HMGB1 is a promising therapeutic agent for lung cancer, damaging cancer cells while reinforcing normal cells.

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The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

Cited by 2 publications

References 101 publications

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats

Box A of HMGB1 Maintains the DNA Gap and Prevents DDR-induced Kidney Injury in D-galactose Induction Rats

The role of Box A of HMGB1 in producing γH2AX-associated DNA breaks in lung cancer

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