Adenosine A_2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils

Abstract

Polydeoxyribonucleotide (PDRN) interacts with the adenosine A 2A -receptor and stimulates vascular endothelial growth factor (VEGF) expression. While it has been indicated that PDRN might accelerate wound healing, its impact on gastric ulcers (GU) is still unknown. We investigated the effects of PDRN on VEGF expression in relation to inflammation and apoptosis in GU by using Mongolian gerbils. GU was induced by injection of acetic acid into the subserosal surface of the stomach. The gerbils in the PDRN-treated groups received daily intraperitoneal injections of PDRN over 2 weeks. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for VEGF, Bax, and Bcl-2 were conducted. Acetic acid injection induced GU, and VEGF expression in the gastric mucosa was enhanced by GU. PDRN treatment decreased ulcer size and led to overexpression of VEGF in GU. Expression of TNF-α, IL-1β, and IL-6 was increased in GU, and PDRN treatment decreased the expression of these cytokines. The numbers of TUNEL-positive and caspase-3-positive cells were increased by GU, while PDRN reduced these numbers. Induction of GU enhanced the ratio of Bax to Bcl-2, while PDRN diminished this ratio. Overexpression of VEGF and inhibition of inflammation and apoptosis by PDRN may be the underlying mechanisms of PDRN action on GU healing.

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

“…Angiogenesis is a pivotal process in all types of wound healing, including gastric and colonic mucosal healing [11,12]. It is regulated by many proangiogenic factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor, and endothelial growth factor.…”

“…A 2A R is involved in the anti-inflammatory pathway and in the VEGF production [17,18]. PDRN inhibits apoptosis and exerts anti-inflammatory effect by suppressing the production of inflammatory cytokines [12,18].…”

Postnatal treadmill exercise attenuates prenatal stress-induced apoptosis through enhancing serotonin expression in aged-offspring rats

“…Higher Bax level and lower Bcl-2 level were also reported in the attention deficit/hyperactivity disorder (ADHD) rats with Purkinje cell loss ( Yun et al, 2014 ). In addition, enhanced Bax to Bcl-2 ratio was observed in the gastric ulcer-induced apoptosis in gerbils ( Jeon et al, 2014 ). In the present study, offspring exposed to prenatal stress exhibited lower level of the Bcl-2 and higher level of Bax in the hippocampus compared to age-matched control rats.…”

Dexmedetomidine alleviates cerebral ischemia-induced short-term memory impairment by inhibiting the expression of apoptosis-related molecules in the hippocampus of gerbils

“…In order to visualize DNA fragmentation, a marker of apoptosis, TUNEL staining was performed using an In Situ Cell Death Detection kit ® (Roche Diagnostics GmbH, Mannheim, Germany) according to the manufacturer's instructions (4,24). The sections were post-fixed in ethanol-acetic acid (2:1), rinsed, then incubated with proteinase K (100 µg/ml).…”

“…In order to visualize the caspase-3 expression, caspase-3 immunohistochemistry was performed as previously described (4,24). The sections were selected from each brain and incubated overnight with caspase-3 antibody (cat.…”