Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

Zickri, Maha Baligh; Aboul-Fotouh, Gihan Ibrahim; Omar, Abeer Ibraheem; El-Shafei, Asmaa; Reda, Ahmed

doi:10.15283/ijsc18002

Cited by 3 publications

(3 citation statements)

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“…it has been reported that Serca2b regulates er stress (19), which is attenuated in pancreatic β-cells (20). A previous study has indicated that SERCA2 exerts protective effects by regulating HG-treated er stress and apoptosis in podocytes (19). Therefore, the present study aimed to investigate the role and function of GAS5 and SERCA2b in DR.…”

Section: Introductionmentioning

confidence: 91%

“…Serca2b is located at the sarcoplasmic reticulum or er membrane of all types of cells and is responsible for maintaining intracellular ca 2+ homeostasis. it has been reported that Serca2b regulates er stress (19), which is attenuated in pancreatic β-cells (20). A previous study has indicated that SERCA2 exerts protective effects by regulating HG-treated er stress and apoptosis in podocytes (19).…”

Section: Introductionmentioning

confidence: 95%

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LncRNA GAS5 suppresses ER stress‑induced apoptosis and inflammation by regulating SERCA2b in HG‑treated retinal epithelial cell

2020

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Hyperglycemia impairs the retinal functions in patients with diabetic retinopathy (dr). downregulation of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) expression in diabetes affects glucose intake and insulin signaling. Sarcoplasmic/endoplasmic reticulum ca 2+ aTPase 2 (Serca2) mediates the regulation of endoplasmic reticulum (er) stress and apoptosis in high glucose (HG)-treated podocytes. Therefore, the present study aimed to investigate the roles of lncRNA GAS5 and SERCA2 in retinal pigment epithelium cells exposed to HG. GAS5 expression levels were detected using reverse transcription-quantitative PCR. In addition, the expression levels of SERCA2b, ER stress-related proteins, pro-inflammatory factors and apoptotic proteins were determined by western blot analysis, eliSa or flow cytometry. The results showed that HG treatment induced er stress in arPe-19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p)-protein kinase R-like ER kinase, p-eukaryotic initiation factor 2α, activating transcription factor 4 and ccaaT/enhancer-binding protein homologous protein. in addition, HG treatment induced apoptosis by increasing Bax, Bad and caspase 12, and by decreasing Bcl-2 levels expression levels. Moreover, HG treatment induced inflammation by upregulating tumor necrosis factor-α, interleukin (IL)-1β and IL-6 expression. However, GAS5 and SERCA2b overexpression significantly decreased ER stress-related apoptosis and inflammation, whereas SERCA2b knockdown significantly reversed the inhibitory effect of GAS5 on ER stress, apoptosis and inflammation. The results of the present study indicated that GAS5 may suppress ER stress-induced apoptosis and inflammation by regulating SERCA2b in HG-treated cells.These data suggested that GAS5 may serve a vital role in the pathogenesis of dr, and it may be considered a potential target for dr therapy.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 95%

LncRNA GAS5 suppresses ER stress‑induced apoptosis and inflammation by regulating SERCA2b in HG‑treated retinal epithelial cell

2020

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“…In that study, analysis of miRNA expression the differentiation of hepatocytes to insulin-producing cells was associated with the BMP/Smad signaling pathway rather than the Wnt/β-catenin signaling pathway [ 76 ]. More recently, transfection of Sarco-ER Ca 2+ -ATPase 2b gene in adipose mesenchymal stem cells exhibited a significant therapeutic effect in a mouse model of type 1 diabetes [ 77 ]. Recent reports also showed the effect of FGF21 gene therapy on a high-fat-diet mouse model where treatment was associated with significant reductions in body weight, adipose tissue hypertrophy, insulin resistance, hepatic steatosis, inflammation, and fibrotic changes [ 78 ].…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Gene Therapy for Pancreatic Diseases: Current Status

Kamimura

Yokoo

Terai

2018

IJMS

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The pancreas is a key organ involved in digestion and endocrine functions in the body. The major diseases of the pancreas include pancreatitis, pancreatic cancer, cystic diseases, pancreatic divisum, islet cell tumors, endocrine tumors, diabetes mellitus, and pancreatic pain induced by these diseases. While various therapeutic methodologies have been established to date, however, the improvement of conventional treatments and establishment of novel therapies are essential to improve the efficacy. For example, conventional therapeutic options, including chemotherapy, are not effective against pancreatic cancer, and despite improvements in the last decade, the mortality rate has not declined and is estimated to become the second cause of cancer-related deaths by 2030. Therefore, continuous efforts focus on the development of novel therapeutic options. In this review, we will summarize the progress toward the development of gene therapies for pancreatic diseases, with an emphasis on recent preclinical studies and clinical trials. We aim to identify new areas for improvement of the current methodologies and new strategies that will lead to safe and effective gene therapeutic approaches in pancreatic diseases.

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