PMID- 32683849 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230222 IS - 1827-1669 (Electronic) IS - 0026-4806 (Linking) VI - 114 IP - 1 DP - 2023 Feb TI - Inhibiting MiR-34alpha reduces retinal cell apoptosis and downstream NF-kappaB pathway in diabetic retinopathy rats through regulating HMGB1 expression. PG - 49-55 LID - 10.23736/S0026-4806.20.06625-2 [doi] AB - BACKGROUND: This is a research aimed to study the effect of micro ribonucleic acid (miR)-34alpha on the retinal cell apoptosis in diabetic retinopathy (DR) rats and its key molecular mechanism. METHODS: Sprague-Dawley rats were randomly divided into healthy group (H group, N.=5), diabetes group (D group, N.=5), diabetes + negative control transfection group (N group, N.=5) and diabetes + miR-34alpha inhibitor transfection group (M group, N.=5). The rat model of diabetes was established via intraperitoneal injection of 2% streptozotocin solution (60 mg/kg). After 72 h, the urine glucose and blood glucose were detected, and the urine glucose above 3+ and the blood glucose concentration >16.7 mmol/L indicated the successful modeling. After the rats were normally fed for 4 months, the changes in expression of miR-34alpha in retinal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR), the pathological changes in retinal tissues were observed via hematoxylin-eosin (HE) staining, and the retinal cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the changes in the number of cells containing active caspase-3 in retinal tissues were determined through immunohistochemistry, and the changes in expressions of caspase-3, high mobility group box 1 (HMGB1) and nuclear factor-kappaB (NF-kappaB) in retinal tissues were determined through Western blotting. RESULTS: Compared with those in H group, the cell density declined, and the cells were arranged disorderly with swelling in each retinal layer, the expression of miR-34alpha in retinal tissues was increased, the retinal cell apoptosis was enhanced, the number of cells containing active caspase-3 in retinal tissues rose, and the expressions of caspase-3, HMGB1 and NF-kappaB in retinal tissues were increased in D group, N group and M group (P<0.05). Compared with those in D group and N group, the cell density rose, and the cells were arranged less disorderly with milder swelling in each retinal layer, the expression of miR-34alpha in retinal tissues declined, the retinal cell apoptosis was weakened, the number of cells containing active caspase-3 in retinal tissues was decreased, and the expressions of caspase-3, HMGB1 and NF-kappaB in retinal tissues were reduced in M group (P<0.05). CONCLUSIONS: Inhibiting miR-34alpha reduces the retinal cell apoptosis in DR rats through regulating the HMGB1 expression and downstream NF-kappaB pathway. FAU - Ma, Yibin AU - Ma Y AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China. FAU - DU, Yunhong AU - DU Y AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China. FAU - Xu, Qian AU - Xu Q AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China. FAU - Bao, Huijing AU - Bao H AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China. FAU - Liu, Zhonglian AU - Liu Z AD - Radiotherapy Center, Taian Oncology Hospital, Taian, China. FAU - Li, Yingchao AU - Li Y AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China. FAU - Liu, Wenjing AU - Liu W AD - Department of Ophthalmology, Taian City Central Hospital, Taian, China - liuwenjing1977@163.com. LA - eng PT - Journal Article DEP - 20200717 PL - Italy TA - Minerva Med JT - Minerva medica JID - 0400732 RN - 0 (NF-kappa B) RN - EC 3.4.22.- (Caspase 3) RN - 0 (Blood Glucose) RN - 0 (HMGB1 Protein) RN - 0 (MicroRNAs) SB - IM MH - Rats MH - Animals MH - *Diabetic Retinopathy MH - NF-kappa B MH - Caspase 3 MH - Blood Glucose MH - *HMGB1 Protein MH - Rats, Sprague-Dawley MH - Apoptosis MH - *MicroRNAs MH - *Diabetes Mellitus EDAT- 2020/07/21 06:00 MHDA- 2023/02/22 06:00 CRDT- 2020/07/21 06:00 PHST- 2020/07/21 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2020/07/21 06:00 [entrez] AID - S0026-4806.20.06625-2 [pii] AID - 10.23736/S0026-4806.20.06625-2 [doi] PST - ppublish SO - Minerva Med. 2023 Feb;114(1):49-55. doi: 10.23736/S0026-4806.20.06625-2. Epub 2020 Jul 17.