• BMB Reports
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• v.40 no.4
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• pp.467-474
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• 2007

Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

• The Journal of the Korean life insurance medical association
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• v.2 no.1
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• pp.218-232
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• 1985

Congenital hereditary disease is in devided into Infantile type and Adult type, Adult type is hidden for many years and keeps normal renal function till middle age. Cyst is stimultaneously made in both sides and becomes lowered in renal function in 30's to 40's. Infantile type is generally born with the big kidneys, renal failure, undergrowth of intrahepatic bile duct. Both infantile and childhood type have ureteral dilatation and portal hypertension In infantile type, it is mostly developed into renal failure, but generally faces death as a result of hepatic disease. The reason of death is that an abnormal condition of recessive autosome affects the liver and kidneys. While the incidence of infantile type is rare as $0.017{\sim}0.07%$ and it is autosomal recessive heredity, Adult type can rarely exist in infantile period. Though it exists in middle period, 50% of patients can live for 2-4 years after the first symptom incidence and 25% can less than 2 years. It is hard to cure completely in medicine and surgery. Three difficulties in familial incidence are comparative decrease of the donor who have no affection on renal transplantation. For another consideration it is to show the family history for several generations. We, the Med. Dept. of Dae Han Kyouk Life Insurance Co. Ltd., used the ultrasonic apparatus in diagnosing the one case of adult type bilateral polycystic kidney and then doubted the family history. As a result of inspecting the family we experienced bilateral polycystic kidney from 3 persons out of 4 who can be inspected. The results are as follows: 1) We could confirm the polycystic kidney from 3 persons out of 4(75%). 2) Then when they came for check up, chief complaint was the pain in all 3 cases(100%). 3) Accompanying disease was hypertension in 2 cases(67%). 4) In early disease incidence, we couldn't observe the specific change in pathological opinion. 5) All 3 cases are not accompanied with cystic lesion in liver, spleen, pancreas.

• Investigative Magnetic Resonance Imaging
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• v.11 no.1
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• pp.39-48
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• 2007

Purpose : To determine the diagnostic accuracy of four different sequences : moderately T2 weighted, two heavily T2-weighted single shot turbo spin-echo sequence and breath-hold axial-2D balanced turbo field-echo sequence(bFFE) for characterization of focal lesions. Materials and Methods : During the 3-month period between June and August 2005, seventy-six patients were proved to have ninety-three focal hepatic lesions on MR imaging. The patients consisted of 49 men and 27 women (age range, 15-75 years; mean age, 56.23 years). All MR images were acquired on a 1.5-T MR using the following sequences: 1. A breath-hold axial T2-weighted single shot turbo spin-echo sequence, 2. a breath-hold axial-2D balanced turbo field-echo sequence. Two radiologists performed quantitative analysis. Another radiologist measured the lesion-to-liver contrast-to-noise ratio at the region-of-interest in the four sequences. Results : There was no significant difference in inter-observer variability between the four sequences. The accuracy for both cyst and malignancy of moderate T2 weighted MRI (echo time: 80 msec) was also highest. There was significant difference for lesion characterization between moderate T2 weighted MRI and balanced steady state procession (p-value: 0.004) in the second reader. For longer echo time, the CNR of cystic lesions were markedly increased in comparison to lesions of other component. Conclusion : The accuracy and inter-observer variability of single shot turbo spin echo T2 weighted sequence was higher than bFFE. Although there was no statically significant difference, moderate T2 weighted MRI (echo time: 80 msec) was more accurate than heavily T2 weighted sequence (echo time: 300 msec). If the results for lesion characterization is equivocal in TE 80, the addition of heavily T2 weighted MRI (echo time: 180 msec) can be helpful.