RESUMO
BACKGROUND: Circular RNA is a key regulator involved in the progression of many human diseases including diabetic nephropathy (DN). However, the role and mechanism of hsa_circ_0037128 in the occurrence and development of DN remains to be explored. METHODS: High glucose (HG)-induced podocytes were used to construct in vitro DN models. The expression of hsa_circ_0037128, microRNA (miR)-31-5p, and Kruppel-like factor 9 (KLF9) was determined using quantitative real-time polymerase chain reaction. The viability and apoptosis of podocytes was measured using cell counting kit 8 assay and flow cytometry. Western blot analysis was performed to examine the protein levels of apoptosis markers and KLF9 in podocytes. Inflammation factors were detected by ELISA assay, and oxidative stress markers were assessed by corresponding Assay Kits. In addition, the interaction between miR-31-5p and hsa_circ_0037128 or KLF9 was verified using dual-luciferase reporter assay and RIP assay. RESULTS: Our data suggested that hsa_circ_0037128 was highly expressed in DN patients and HG-induced podocytes. In HG-induced podocytes, hsa_circ_0037128 knockdown could alleviate HG-induced podocytes injury. In the term of mechanism, hsa_circ_0037128 could sponge miR-31-5p to upregulate KLF9. MiR-31-5p inhibitor could reverse the negative regulation of hsa_circ_0037128 silencing on HG-induced podocytes injury. Also, miR-31-5p relieved HG-induced podocytes injury, and this effect also could be reversed by KLF9 overexpression. CONCLUSION: In summary, our data showed that hsa_circ_0037128 could promote HG-induced podocytes injury via regulating miR-31-5p/KLF9 axis, showing that hsa_circ_0037128 might be a target for DN treatment.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Glucose , Fatores de Transcrição Kruppel-Like , MicroRNAs , Podócitos , Apoptose/genética , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Glucose/administração & dosagem , Glucose/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Podócitos/metabolismo , Podócitos/patologia , RNA Circular/genética , RNA Circular/metabolismoRESUMO
The development of postmenopausal osteoporosis is thought to be closely related to oxidative stress. Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase (SOD) mimetic, could protect osteoblasts from cytotoxicity and dysfunction caused by oxidative stress. However, it is still unclear whether MnTBAP has effect on the development of postmenopausal osteoporosis. Here, we demonstrated that MnTBAP can inhibit bone mass loss and bone microarchitecture alteration, and increase the number of osteoblasts while reducing osteoclasts number, as well as improve the BMP-2 expression level in ovariectomized rat model. Additionally, MnTBAP can also prevent oxidative stress status up-regulation induced by ovariotomy and hydrogen peroxide (H2O2). Furthermore, MnTBAP reduced the effect of oxidative stress on osteoblasts differentiation and increased BMP-2 expression levels with a dose-dependent manner, via reducing the levels of mitochondrial oxidative stress in osteoblasts. Taken together, our findings provide new insights that MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts, and maybe a potential drug in postmenopausal osteoporosis therapy.
Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Metaloporfirinas/uso terapêutico , Mitocôndrias/metabolismo , Osteoblastos/metabolismo , Ovariectomia , Estresse Oxidativo , Animais , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Peróxido de Hidrogênio/toxicidade , Metaloporfirinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.
