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Differentiation of Pancreatic Ductal Epithelial Cells into Insulin Like Cell Clusters in Chronic Pancreatitis

Open Journal of Endocrine and Metabolic Diseases 2015年第12期5卷 177-183页

作者： Pondugala Pavan Kumar gaddipati radhika G. Venkat Rao D. Nageshwar Reddy M. Sasikala Asian Health Care Foundation Somajiguda Hyderabad India Asian Institute of Gastroenterology Somajiguda Hyderabad India

Background/Aim: Islet regeneration in chronic pancreatitis (CP) is relevant for managing the associated loss of endocrine function. Because ductal epithelial cells were earlier demonstrated to differentiate into pancreatic endocrine mass, we evaluated their proliferation and differentiation in chronic pancreatitis. Methods: Pancreatic ducts were obtained from surgically resected pancreata of 12 patients with chronic pancreatitis and 15 control subjects. CK19 positive ductal cells were evaluated for their proliferating and differentiating abilities upon immunostaining with Ki 67 and hormone positivity for insulin and glucagon, apart from monitoring Pdx 1 expression. Results: In comparison to the controls, a greater number of proliferating pancreatic ductal epithelial cells (PDECs) were observed under conditions of CP. The increase in Pdx1 expressing PDECs (22%) and proliferating Pdx1 expressing PDECs (30%) was significant (P < 0.04). Number of cells expressing insulin/glucagon in the exocrine ducts increased significantly in CP as compared to controls (P ?β?cell mass adjacent to the ducts increased by 28%.?Conclusion: Enhanced capability of PDECs to proliferate and differentiate into endocrine mass suggests that PDECs form a source of progenitors for cell based therapy in chronic pancreatitis.

关键词： Chronic Pancreatitis Ductal Epithelial Cells Islet Like Clusters Cell Differentiation

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EGR1 is essential for transcriptional regulation of BMPR2

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American Journal of Molecular Biology 2011年第3期1卷 131-139页

作者： radhika gaddipati James D. West James E. Loyd Thomas Blackwell Kirsten A. Lane Nicole M. Lane Kirk B. Lane 不详

In this study, RLM-RACE was used to identify the transcriptional start site 387 bp upstream of the translational start. Evolutionarily conserved transcription factor binding sites were identified, and a series of luciferase reporter constructs driven by BMPR2 promoter elements used to determine their functional relevance. We found the promoter area from 983 bp to 90 bp upstream of the transcriptional start gave maximal activity, greater than longer constructs, with an area between 570 bp and 290 bp upstream of the transcriptional start containing an important repressor element. To characterize this repressor, we used a combination of EMSA, mutation of the EGR1 binding site, transfection with EGR1 and NAB1 constructs, and mutation of the NAB1 binding site within the EGR1 protein. From this we conclude that EGR1 is essential to BMPR2 transcription, but that NAB1 binding to EGR1 causes it to act as a repressor.

关键词： Transcription BMPR2 Regulation EGR1 NAB1 Pulmonary Hypertension

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Identification of circulating CD90^+ CD73^+ cells in cirrhosis of liver

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World Journal of Stem Cells 2011年第7期3卷 63-69页

作者： Mitnala Sasikala Pugazhelthi Surya gaddipati radhika Pondugala Pavan Kumar Mekala Subba Rao Rathindra Mohan Mukherjee Padaki Nagaraja Rao D Nageshwar Reddy Institute of Basic Sciences and TranslationalResearch Asian Health Care Foundation Asian Institute of Gastroenterology

AIM:To identify circulating CD90 + CD73 + CD45 cells and evaluate their in vitro proliferating ***:Patients with cirrhosis(n=43),and healthy volunteers(n=40)were recruited to the *** cells were isolated and cultured from the peripheral blood of controls and cirrhosis ***-like cells that appeared in cultures were analyzed for morphological features,enumerated by flow cytometry and confirmed by immunocytochemistry(ICC).Colony forming efficiency(CFE)of these cells was assessed and expressed as a ***:In comparison to healthy volunteers,cells obtained from cirrhotic patients showed a significantincrease(P<0.001)in the percentage of CD90+CD73+ CD45 cells in *** cells also showed 10 fold increases in *** cytometry and ICC confirmed that the proliferating cells expressed CD90 + CD73 + in the cultures from cirrhosis ***:These results indicate the presence of circulating CD90 + CD73 + CD45 cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate.

关键词： CD90+ CD73+ CD45 cells Liver cirrhosis Proliferation Colony forming efficiency

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EGR1 is essential for transcriptional regulation of BMPR2

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American Journal of Molecular Biology（美国分子生物学期刊） 2011年第3期

作者： radhika gaddipati James D. West James E. Loyd Thomas Blackwell Kirsten A. Lane Nicole M. Lane Kirk B. Lane

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