1.Inositol 1,4,5-triphosphate receptor 3 promotes renal cyst development in autosomal dominant polycystic kidney disease.
Zhi-Wei QIU ; Ming LIU ; Hong ZHOU ; Bao-Xue YANG
Acta Physiologica Sinica 2023;75(3):328-338
The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.
Animals
;
Dogs
;
Mice
;
Cysts/genetics*
;
Inositol 1,4,5-Trisphosphate Receptors/pharmacology*
;
Kidney/metabolism*
;
Polycystic Kidney Diseases/metabolism*
;
Polycystic Kidney, Autosomal Dominant/drug therapy*
;
Madin Darby Canine Kidney Cells
2.A Case of Cystadenocarcinoma of the Pancreas in a Patient with Autosomal Dominant Polycystic Kidney Disease.
Soo Youn LEE ; Young Jun YANG ; Dong Seok JANG ; Young Mo LEE ; Ki Ryang NA ; Byung Seok LEE ; Kang Wook LEE ; Young Tai SHIN
Korean Journal of Nephrology 2007;26(4):465-468
Polycystic kidney disease is an autosomal dominant disease that may be associated with liver and pancretic cysts. Mitral valve prolapse and intracranial berry aneurysms are also well-known manifestations of autosomal dominant polycystic kidney disease (ADPKD). Cystadenocarcinoma of the pancreas is uncommon and accounts for only 1% of primary pancreatic malignancies. Few cases were reported to have an association of ADPKD and pancreatic malignancies. We report a 63-year-old man with ADPKD who was admitted to our hospital with anorexia and severe weight loss. After abdominal CT and histologic examination, he was diagnosed as pancreatic cystadenocarcinoma with lung, spleen, and liver metastasis. To prolong the life of the patient, we tried gemcitabine and cisplatin combination chemotherapy. But the patient died 2 months after diagnosis due to the disease progression.
Anorexia
;
Cisplatin
;
Cystadenocarcinoma*
;
Diagnosis
;
Disease Progression
;
Drug Therapy, Combination
;
Humans
;
Intracranial Aneurysm
;
Liver
;
Lung
;
Middle Aged
;
Mitral Valve Prolapse
;
Neoplasm Metastasis
;
Pancreas*
;
Pancreatic Neoplasms
;
Polycystic Kidney Diseases
;
Polycystic Kidney, Autosomal Dominant*
;
Spleen
;
Tomography, X-Ray Computed
;
Weight Loss
3.Successfully Treated Escherichia coli-Induced Emphysematous Cyst Infection with Combination of Intravenous Antibiotics and Intracystic Antibiotics Irrigation in a Patient with Autosomal Dominant Polycystic Kidney Disease.
Hyunsuk KIM ; Hayne CHO PARK ; Sunhwa LEE ; Jungsil LEE ; Chungyun CHO ; Dong Ki KIM ; Young Hwan HWANG ; Kook Hwan OH ; Curie AHN
Journal of Korean Medical Science 2013;28(6):955-958
A 62-yr-old woman with an autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital for further evaluation of intermittent fever, nausea and left flank discomfort. The computed tomography (CT) scan revealed a gas-forming, infectious cyst of approximately 8.1 cm in size in left kidney lower pole. Escherichia coli was identified from the cyst fluid culture examination. Her symptoms improved only after the concomitant use of intravenous ciprofloxacin and an intracystic irrigation of ciprofloxacin through a percutaneous cystostomy drainage. Our case presents the successfully treated emphysematous cyst infection with combination of intravenous antibiotics and intracystic antibiotic therapy instead of surgical management.
Anti-Bacterial Agents/*therapeutic use
;
Ciprofloxacin/*therapeutic use
;
Cystostomy
;
Cysts/microbiology
;
Escherichia coli Infections/complications/*drug therapy
;
Female
;
Humans
;
Injections, Intravenous
;
Middle Aged
;
Polycystic Kidney, Autosomal Dominant/complications/*diagnosis
;
Therapeutic Irrigation
;
Tomography, X-Ray Computed