1.Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis
Biomolecules & Therapeutics 2024;32(3):291-300
Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.
2.Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis
Biomolecules & Therapeutics 2024;32(3):291-300
Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.
3.Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis
Biomolecules & Therapeutics 2024;32(3):291-300
Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.
4.Suppression of Foxo3-Gatm by miR-132-3p Accelerates Cyst Formation by Up-Regulating ROS in Autosomal Dominant Polycystic Kidney Disease
Seonju CHOI ; Do Yeon KIM ; Yejin AHN ; Eun Ji LEE ; Jong Hoon PARK
Biomolecules & Therapeutics 2021;29(3):311-320
Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1 f/f :HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of FOXO3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.
5.Suppression of Foxo3-Gatm by miR-132-3p Accelerates Cyst Formation by Up-Regulating ROS in Autosomal Dominant Polycystic Kidney Disease
Seonju CHOI ; Do Yeon KIM ; Yejin AHN ; Eun Ji LEE ; Jong Hoon PARK
Biomolecules & Therapeutics 2021;29(3):311-320
Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1 f/f :HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of FOXO3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.
6.Perception to the dietary guidelines for Koreans among Korean adults based on sociodemographic characteristics and lifestyle
Yejin YOON ; Soo Hyun KIM ; Hyojee JOUNG ; Seoeun AHN
Journal of Nutrition and Health 2023;56(6):742-755
Purpose:
This study aimed to investigate the perceptions of the dietary guidelines for Koreans (DGK) among Korean adults based on sociodemographic and lifestyle factors.
Methods:
A total of 514 Korean adults aged 19–64 years completed a self-administered online questionnaire assessing their perceptions of DGK, sociodemographic and lifestyle factors, and subjective assessments regarding the importance of 11 nutrients and 16 food groups. The differences in the perceptions of DGK according to the characteristics of the participants were analyzed using t-tests or ANOVA. Additionally, the differences in the subjective assessments of nutrients and food groups according to the perceptions of DGK were examined using t-tests.
Results:
The awareness of DGK was significantly higher among participants aged 50–64 years, living in single-person households, who were physically active, with a lower frequency of eating out, and with a higher interest in dietary information (p < 0.05 for all). The understanding of DGK was significantly higher among participants aged 19–29 years, females, individuals who were under or normal weight, non-smokers, those who selfevaluated their diet as healthy, and those with a high interest in dietary information (p < 0.05 for all). Additionally, the applicability of DGK was significantly higher among participants aged 50–64 years, who were physically active, who self-evaluated their diet as healthy, and who had a high interest in dietary information (p < 0.05 for all). Participants with a higher perception of DGK tended to attribute greater importance to most nutrients and food groups compared to those with a lower perception level. However, processed meat and foods, beverages, and alcoholic drinks consistently received lower importance ratings compared to other nutrients and food groups, regardless of the perception level.
Conclusion
This research suggests that the perceptions of DGK among Korean adults may vary depending on sociodemographic and lifestyle factors. Consequently, there is a need to customize and diversify the methods for providing dietary guidelines.
7.Comparative Analysis of Anticancer and Antibacterial Activities among Seven Trametes Species
Ha Thi Kim NGUYEN ; Jiwon LEE ; Yejin PARK ; Hyon Jin PARK ; Soon Kil AHN ; Jae Kwang KIM ; Dong-Ku KANG ; Minkyeong KIM ; Chorong AHN ; Changmu KIM ; Jaehyuk CHOI
Mycobiology 2023;51(4):256-263
Species in the genus Trametes (Basidiomycota, Polyporales) have been used in natural medicine for a long time. Many studies reported that mycelia or fruiting bodies of Trametes spp. exhibited effects of antioxidant, anti-inflammatory, anticancer, and antimicrobial activities.However, comparative analysis in this genus is scarce due to limitation of morphological identification and the sample number. In this study, the 19 strains of seven Trametes species were chosen to generate a five-gene-based phylogeny with the 31 global references. In addition, 39 culture extracts were prepared for 13 strains to test for anticancer and antibacterial activities. Strong anticancer activities were found in several extracts from T. hirsuta and T. suaveolens. Anticancer activities of T. suaveolens, T. cf. junipericola and T. trogii were first described here. The antibacterial ability of T. versicolor and T. hirsuta extracts has been confirmed. The antibacterial activities of T. suaveolens have been reported at the first time in this study. These results suggest an efficient application of the genus Trametes as the drug resources especially for anticancer agents.
8.Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study.
Sun Ha JEE ; Chul Woo AHN ; Jong Suk PARK ; Chang Gyu PARK ; Hyon Suk KIM ; Sang Hak LEE ; Sungha PARK ; Myoungsook LEE ; Chang Beom LEE ; Hye Soon PARK ; Heejin KIMM ; Sung Hee CHOI ; Jidong SUNG ; Seungjoon OH ; Hyojee JOUNG ; Sung Rae KIM ; Ho Joong YOUN ; Sun Mi KIM ; Hong Soo LEE ; Yejin MOK ; Eunmi CHOI ; Young Duk YUN ; Soo Jin BAEK ; Jaeseong JO ; Kap Bum HUH
Diabetes & Metabolism Journal 2013;37(4):252-261
BACKGROUND: Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. METHODS: A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. RESULTS: Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. CONCLUSION: A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.
Adiponectin
;
Body Mass Index
;
Cohort Studies
;
Confounding Factors (Epidemiology)
;
Diabetes Mellitus
;
Fasting
;
Female
;
Follow-Up Studies
;
Glucose
;
Humans
;
Incidence
;
Male
;
Proportional Hazards Models
;
Prospective Studies
;
Republic of Korea
;
Waist Circumference