Article
Medicine, General & Internal
Qi Ren, Shengyou Yu, Huasong Zeng, Huimin Xia
Summary: Podocytes' specialized role in maintaining the filtration barrier is regulated, in part, by the phosphatase and tensin homolog (PTEN). This study investigated the role of PTEN in podocyte injury induced by puromycin aminonucleoside (PAN) and the potential protective effects of dexamethasone (DEX) through the PTEN/PI3K/Akt signaling pathway. The findings suggest that targeting PTEN could be a promising therapeutic strategy against podocyte injury.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Xiang Li, Kuangqi Chen, Zixi Wang, Jiayuan Li, Xiawei Wang, Chen Xie, Jianping Tong, Ye Shen
Summary: Corneal diseases affect millions of people worldwide and current treatments have limitations. Activation of the mTOR signaling pathway is involved in the pathogenesis of various corneal diseases, and inhibition of mTOR with rapamycin has shown promising outcomes, indicating the potential of mTOR as a therapeutic target.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Cell Biology
Nadia Bouhamdani, Dominique Comeau, Sandra Turcotte
Summary: Lysosomes have been revealed as crucial multifaceted signaling organelles rather than mere waste bags through research in the past 15 years. They play roles in anti-cancer drug resistance and are involved in a series of molecular and functional changes during malignant transformation leading to tumor aggression, angiogenesis, and metastases. Targeting lysosomes in cancer may lead to the development of new and effective targeted therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cheng Qian, Jiayue Lu, Xiajing Che, Lulin Min, Minzhou Wang, Ahui Song, Renhua Lu, Leyi Gu, Kewei Xie
Summary: Diabetic nephropathy is a major cause of chronic renal failure worldwide. In this study, increased Adenosine triphosphate (ATP) content was found in the urine of diabetic mice. The expression of purinergic P2X7 receptor (P2X7R) was significantly increased in the renal cortex of wild-type diabetic mice and partially co-localized with podocytes. P2X7R inhibition restored podocyte autophagy and may be a potential treatment for diabetic nephropathy.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Neurosciences
Meng- Zhao, Houting Lv, Na Yang, Guang-Hua Peng
Summary: The study investigated the mechanism of retinal photoreceptor degeneration by establishing a stable retinitis pigmentosa (RP) model. It was found that activation of mTOR may be associated with RP, and the use of mTOR inhibitor rapamycin improved retinal function and photoreceptor thickness and morphology, possibly by activating autophagy to protect retinal photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Dominik Spitz, Maria Comas, Lea Gerstner, Severine Kayser, Martin Helmstaedter, Gerd Walz, Tobias Hermle
Summary: Both mTOR signaling and autophagy play important roles in regulating podocyte homeostasis, regeneration, and aging, as well as in glomerular diseases. This study used Drosophila nephrocytes as a podocyte model and found that inhibition of mTOR signaling led to increased spacing between slit diaphragms. Activation or inhibition of mTOR signaling both resulted in decreased nephrocyte function, indicating a delicate balance of signaling activity is required for proper function. Furthermore, mTOR positively regulated cell size, survival, and the subcortical actin network, while basal autophagy in nephrocytes was necessary for survival and limited the expression of nephrin, but did not directly affect slit diaphragm formation or endocytic activity. Excessive, mTOR-dependent autophagy was primarily responsible for slit diaphragm misspacing. Overall, this study established an invertebrate podocyte model for exploring the role of mTOR signaling and autophagy, and revealed a direct regulation of slit diaphragm architecture by the mTOR/autophagy pathway.
Article
Cell Biology
Tianqi Xu, Shannon Nicolson, Jarrod J. Sandow, Sonia Dayan, Xin Jiang, Jantina A. Manning, Andrew Webb, Sharad Kumar, Donna Denton
Summary: Macroautophagy/autophagy is a critical lysosomal degradative pathway that plays a key role in maintaining cellular homeostasis. Studies on Drosophila larval midguts reveal that peptidase proteins are involved in autophagy-dependent cell death. Cathepsin enzymes, particularly Cp1, are essential for proper degradation and turnover of autophagosomes, indicating their crucial role in maintaining basal autophagy flux.
Article
Medicine, Research & Experimental
Xinying Zhang, Li Zhang, Zhe Chen, Siwei Li, Bingbing Che, Ningning Wang, Junting Chen, Changqing Xu, Can Wei
Summary: This study found that the progression of diabetic nephropathy is influenced by the polyamine metabolic pool, particularly the decrease in spermine content. High glucose can lead to increased kidney weight, abnormal kidney function, increased urinary albumin excretion, mesangial thickening, and loss or fusion of podocytes.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Mariana Borsa, Sandrine Obba, Felix C. Richter, Hanlin Zhang, Thomas Riffelmacher, Joana Carrelha, Ghada Alsaleh, Sten Eirik W. Jacobsen, Anna Katharina Simon
Summary: This study investigates the importance of autophagy in stem cells and finds that autophagy deficiency leads to stem cell loss and bone marrow failure, while inhibition of MTOR can rescue this loss and improve stem cell function.
Article
Pharmacology & Pharmacy
Martina P. Morawe, Fan Liao, Willi Amberg, Jeroen van Bergeijk, Rui Chang, Mary Gulino, Caitlin Hamilton, Carolin Hoft, Casey Lumpkin, Bryan Mastis, Emily McGlame, Judith Nuber, Christian Plaas, Brinda Ravikumar, Kaushambi Roy, Marion Schanzenbaecher, Joseph Tierno, Viktor Lakics, Tammy Dellovade, Matthew Townsend
Summary: In this study, the researchers aimed to reduce tau pathology in Alzheimer's Disease by activating mTOR-dependent autophagy. They found that mTOR inhibitors could effectively reduce tau pathology, with PQR530 showing better results even when treatment was started after the onset of pathology. The researchers concluded that intermittent dosing of mTOR inhibitors can have a disease-modifying effect in AD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Qian Wu, Qianyu Lv, Xiao'an Liu, Xuejiao Ye, Linlin Cao, Manshi Wang, Junjia Li, Yingtian Yang, Lanlan Li, Shihan Wang
Summary: Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases. The activation of the mechanistic/mammalian target of rapamycin (mTOR) is closely associated with the risk of AS. The mTOR signaling pathway contributes to AS progression through regulating autophagy, cell senescence, immune response, and lipid metabolism. Botanical drugs and their functional compounds have shown anti-AS effects by modulating the activity of the mTOR signaling pathway. This review summarizes the pathogenesis of AS based on the mTOR signaling pathway and recent advances in natural compounds to inhibit the mTOR signaling pathway and delay AS development, providing a new perspective on the mechanisms and precision treatments of AS.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yoong Mond Teh, Siti Aisyah Mualif, Soo Kun Lim
Summary: Podocytes play an important role in maintaining kidney function, and their injury can lead to proteinuria in various kidney diseases. Podocyte autophagy has become a therapeutic target for improving podocyte injury, with sirtuin-1 playing a crucial role in this process.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Neslihan Pinar Ozates, Fatma Sogutlu, Ferzan Lerminoglu, Busra Demir, Cumhur Gunduz, Behrouz Shademan, Cigir Biray Avci
Summary: Breast cancer is the most common cancer in women and aberrations in the PI3K/AKT/mTOR pathway present in more than 70% of breast cancer cases have become a therapeutic target. AZD3463, as an anti-cancer agent, induces apoptosis and autophagy in breast cancer cells, reducing cell survival and proliferation. The combination of rapamycin and AZD3463 can increase the expression of certain genes related to apoptosis and decrease genes associated with cell survival, reducing resistance to treatment and leading to cancer cell apoptosis.
Review
Biochemistry & Molecular Biology
Seo Hyeong Park, Won Hoon Choi, Min Jae Lee
Summary: mTOR, a mechanistic target, plays a crucial role in regulating cellular homeostasis and cell growth, including autophagy and proteasome activity. Inhibition of mTORC1 can induce autophagy, while proteasomes provide amino acids necessary for protein synthesis. Understanding the connection between mTORC1 activity and proteasome function is important for the evaluation of mTORC1 inhibitors as therapeutic treatments.
Article
Biochemistry & Molecular Biology
Xuejing Zhu, Dan Gao, Vittorio Albertazzi, Jianyong Zhong, Li-Jun Ma, Liping Du, Yu Shyr, Valentina Kon, Hai-Chun Yang, Agnes B. Fogo
Summary: The study found that long-term treatment with high-dose angiotensin receptor blocker (ARB) and nonspecific antihypertensive therapy can ameliorate the progression of glomerulosclerosis. Among them, ARB treatment showed superior preservation of podocyte integrity, decreased proteinuria and aldosterone levels, and higher survival rate in uremic rats compared to other treatment methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Yoshitaka Kubota, Minoru Takemoto, Toshibumi Taniguchi, Sei-ichiro Motegi, Akira Taniguchi, Hironori Nakagami, Yoshiro Maezawa, Masaya Koshizaka, Hisaya Kato, Seijiro Mori, Kazuhisa Tsukamoto, Masafumi Kuzuya, Koutaro Yokote
Summary: Skin ulcers in patients with Werner syndrome are often found at the distal one-third of the lower legs, with calluses being a common issue. Addressing calluses for treatment or prevention of ulcers is crucial for improving the quality of life for these patients.
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2021)
Article
Geriatrics & Gerontology
Kazuhisa Tsukamoto, Minoru Takemoto, Yoshitaka Kubota, Toshibumi Taniguchi, Sei-ichiro Motegi, Akira Taniguchi, Hironori Nakagami, Yoshiro Maezawa, Masaya Koshizaka, Hisaya Kato, Seijiro Mori, Masafumi Kuzuya, Koutaro Yokote
Summary: The characteristics of dyslipidemia and fatty liver in patients with Werner syndrome in Japan were examined by searching case reports. Treatment methods were not well described in the reports, so detailed data from 12 cases were analyzed at Chiba University.
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2021)
Article
Geriatrics & Gerontology
Akira Taniguchi, Yasuhito Tanaka, Minoru Takemoto, Yoshitaka Kubota, Toshibumi Taniguchi, Sei-ichiro Motegi, Hironori Nakagami, Yoshiro Maezawa, Masaya Koshizaka, Hisaya Kato, Kazuhisa Tsukamoto, Seijiro Mori, Masafumi Kuzuya, Koutaro Yokote
Summary: The study clarified the diagnostic value of calcification in the Achilles tendon for Werner syndrome by comparing patients with and without the syndrome. The results showed a significantly higher frequency of Achilles tendon calcification in patients with Werner syndrome, suggesting it could be included in diagnostic criteria for the syndrome.
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2021)
Article
Endocrinology & Metabolism
Ryoichi Ishibashi, Yusuke Baba, Kyoka Kakinuma, Atsushi Takasaki, Chihiro Hiraga, Tomomi Harama, Tetsuya Yamamoto, Susumu Nakamura, Masaya Koshizaka, Yoshiro Maezawa, Daigaku Uchida, Fumitaka Okajima
Summary: The study found that the use of SGLT2 inhibitors in patients with type 1 diabetes can improve treatment satisfaction and may improve glycemic variability, while caution should be taken to avoid severe side effects.
Article
Genetics & Heredity
Takahiro Ishikawa, Minoru Takemoto, Yoshihiro Akimoto, Aki Takada-Watanabe, Kunimasa Yan, Kenichi Sakamoto, Yoshiro Maezawa, Miyuki Suguro, Liqun He, Karl Tryggvason, Christer Betsholtz, Koutaro Yokote
Summary: A novel podocyte-expressed protein R3h domain containing-like (R3hdml) was identified, which inhibits podocyte apoptosis by suppressing TGF-beta-mediated p38 MAPK signaling. Overexpression of R3hdml ameliorated albuminuria in STZ-induced diabetes mice, suggesting it may be a potential therapeutic strategy for diabetic nephropathy.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Endocrinology & Metabolism
Yusuke Baba, Ryoichi Ishibashi, Atsushi Takasaki, Chiho Ito, Atsuko Watanabe, Megumi Tokita, Miwako Meguro, Tomomi Harama, Kiichi Hirayama, Tetsuya Yamamoto, Susumu Nakamura, Masaya Koshizaka, Yoshiro Maezawa, Daigaku Uchida, Fumitaka Okajima
Summary: SGLT2 inhibitors have beneficial effects on reducing fat mass and glycemic variabilities in patients with type 1 diabetes mellitus, but concerns exist regarding the reduction of skeletal muscle, especially in lean patients.
Article
Endocrinology & Metabolism
Kenji Takeda, Hiraku Ono, Ko Ishikawa, Tomohiro Ohno, Jin Kumagai, Hidetoshi Ochiai, Ai Matumoto, Hidetaka Yokoh, Yoshiro Maezawa, Koutaro Yokote
Summary: The study demonstrates that SGLT2 inhibitors in the CNS can increase food intake, potentially regulating it through AMPK phosphorylation in the lateral hypothalamic area.
BMJ OPEN DIABETES RESEARCH & CARE
(2021)
Article
Multidisciplinary Sciences
Benjamin R. Thomson, Pan Liu, Tuncer Onay, Jing Du, Stuart W. Tompson, Sol Misener, Raj R. Purohit, Terri L. Young, Jing Jin, Susan E. Quaggin
Summary: Primary congenital glaucoma (PCG) is a severe disease with increased intraocular pressure, and variants in ANGPT1 or SVEP1 have been identified as risk alleles. Deletion of these genes induces glaucoma in mice, and activation of ANGPT1-TEK signaling ameliorates disease progression in mouse models.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Jing Du, Benjamin R. Thomson, Tuncer Onay, Susan E. Quaggin
Summary: Studies have shown that Tie1 plays a crucial role in the development and function of Schlemm's canal. Loss of Tie1 leads to hypomorphic Schlemm's canal and elevated intraocular pressure. Therefore, Tie1 may be a novel target for future glaucoma therapies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Hematology
Hisaya Kato, Yoshiro Maezawa, Dai Nishijima, Eisuke Iwamoto, June Takeda, Takashi Kanamori, Masaya Yamaga, Tatsuzo Mishina, Yusuke Takeda, Shintaro Izumi, Yutaro Hino, Hiroyuki Nishi, Jun Ishiko, Masahiro Takeuchi, Hiyori Kaneko, Masaya Koshizaka, Naoya Mimura, Masafumi Kuzuya, Emiko Sakaida, Minoru Takemoto, Yuichi Shiraishi, Satoru Miyano, Seishi Ogawa, Atsushi Iwama, Masashi Sanada, Koutaro Yokote
Summary: Werner syndrome (WS) is associated with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), and patients are prone to TP53 gene mutations and chromosomal abnormalities involving TP53, rather than other common mutations related to MDS/AML. These mutations may be related to WRN gene mutations and p53 insufficiency, leading to complex chromosomal abnormalities and the development of myeloid malignancies.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Thuy N. Vien, My C. Ta, Louise F. Kimura, Tuncer Onay, Paul G. DeCaen
Summary: In this study, the researchers found that PKD2L1 localizes and functions as a Ca2+ channel in the primary cilia of hippocampal neurons. Loss of PKD2L1 expression disrupts primary ciliary maturation, weakens neuronal high-frequency excitability, and leads to seizure susceptibility and autism spectrum disorder-like behavior in mice. The disproportionate impairment of interneuron excitability suggests that circuit disinhibition underlies the neurophenotypic features of these mice. These findings identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Endocrinology & Metabolism
Shintaro Ide, Yoshiro Maezawa, Koutaro Yokote
JOURNAL OF DIABETES INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Yoshiro Maezawa, Yusuke Endo, Satomi Kono, Tomohiro Ohno, Yuumi Nakamura, Naoya Teramoto, Ayano Yamaguchi, Kazuto Aono, Takuya Minamizuka, Hisaya Kato, Takahiro Ishikawa, Masaya Koshizaka, Minoru Takemoto, Toshinori Nakayama, Koutaro Yokote
Summary: Psoriasis, a chronic inflammatory skin disease, is associated with obesity and myocardial infarction. Obesity-induced changes in lipid metabolism promote the differentiation of T helper 17 (Th17) cells, leading to chronic inflammation. This study found that weight loss through diet and exercise decreased Th17 cells and improved psoriasis in an obese patient with type 2 diabetes. This supports the hypothesis that obesity increases Th17 cells and chronic inflammation, contributing to psoriasis and atherosclerosis.
JOURNAL OF DIABETES INVESTIGATION
(2023)
Article
Physiology
Michael D. Donnan, Dilip K. Deb, Tuncer Onay, Rizaldy P. Scott, Eric Ni, Yalu Zhou, Susan E. Quaggin
Summary: Targeting VEGFR-3 in kidney lymphatics has been proposed as a method to treat kidney disease. However, expression of VEGFR-3 is not lymphatic-specific. We demonstrated developmental expression of VEGFR-3 in glomerular endothelial cells, with loss of Vegfr-3 leading to malformation of glomerular capillary loops. Furthermore, we showed that VEGFR-3 attenuates VEGFR-2 activity in glomerular endothelial cells independent of paracrine VEGF-C signaling. Together, these data provide valuable information for therapeutic development targeting these pathways.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Urology & Nephrology
Gal Finer, Yoshiro Maezawa, Shintaro Ide, Tuncer Onay, Tomokazu Souma, Rizaldy Scott, Xiaoyan Liang, Xiangmin Zhao, Gaurav Gadhvi, Deborah R. Winter, Susan E. Quaggin, Tomoko Hayashida
Summary: Kidney formation requires interactions between various cell types, with interstitial progenitor cells playing a crucial role. Tcf21 in Foxd1+ interstitial progenitors is shown to regulate stromal formation and differentiation through interaction with beta-catenin. The absence of Tcf21 leads to decreased stromal cell proliferation and defective differentiation of interstitial cells in the kidney.
