Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Pharmacology & Pharmacy
Aqsa Ashfaq, Myriam Meineck, Andrea Pautz, Ebru Arioglu-Inan, Julia Weinmann-Menke, Martin C. Michel
Summary: A systematic review of studies on SGLT2 inhibitors in rodent models of diabetes showed that these inhibitors not only improved glycemic control but also had various beneficial effects on renal function. These nephroprotective effects were observed in different animal models of type 1 and type 2 diabetes/obesity. SGLT2 inhibitors had positive effects on lipid metabolism, blood pressure, glomerulosclerosis, renal tubular fibrosis, apoptosis, oxidative stress, and inflammation, which are important pathomechanisms for atherosclerosis and renal health. However, more data on female animals and direct comparative studies with other anti-diabetic compounds are needed.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Zhiwei Qiu, Jinzhao He, Guangying Shao, Jiaqi Hu, Xiaowei Li, Hong Zhou, Min Li, Baoxue Yang
Summary: This study identified obacunone as a potential therapeutic drug for ADPKD, as it inhibited cyst formation and expansion and regulated lipid peroxidation and cell proliferation pathways.
Article
Medicine, Research & Experimental
Ignacio Prieto, Maria Kavanagh, Luna Jimenez-Castilla, Marisa Pardines, Iolanda Lazaro, Isabel Herrero del Real, Monica Flores-Munoz, Jesus Egido, Oscar Lopez-Franco, Carmen Gomez-Guerrero
Summary: Diabetic kidney disease (DKD) is a common complication of diabetes, in which inflammation and oxidative stress play important roles. This study reveals the involvement of miR-155-5p and SOCS1 in the regulation of the JAK/STAT pathway, highlighting their potential as therapeutic targets for DKD.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Endocrinology & Metabolism
Panai Song, Yinyin Chen, Zhiwen Liu, Hong Liu, Li Xiao, Lin Sun, Jiali Wei, Liyu He
Summary: This study found that the expression of MALAT1, LIN28A and Nox4 was increased in diabetic nephropathy tissues and cells treated with high glucose. Overexpression of these genes led to increased cell apoptosis, oxidative stress, and inflammation, while knockdown of them had the opposite effect. Furthermore, MALAT1 interacted directly with LIN28A and facilitated the interaction between LIN28A and Nox4, stabilizing Nox4 mRNA. Our findings provide potential therapeutic targets for diabetic nephropathy.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Medicine, Research & Experimental
Jakob A. Ostergaard, Jay C. Jha, Arpeeta Sharma, Aozhi Dai, Judy S. Y. Choi, Judy B. de Haan, Mark E. Cooper, Karin Jandeleit-Dahm
Summary: In a clinically relevant interventional model of established diabetic kidney disease (DKD), NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, the use of MCC950 in diabetic mice led to increased renal inflammation, macrophage infiltration, oxidative stress, mesangial expansion, and glomerulosclerosis.
Article
Immunology
Paramarajan Piranavan, Andras Perl
Summary: The study showed that sirolimus is well tolerated and effective in controlling renal and non-renal manifestations of SLE over the long term, reducing anti-DNA antibody levels and steroid use while increasing complement levels. Adverse effects were minimal, with only a small number of patients experiencing mouth sores, headaches, and gastrointestinal discomfort, leading to discontinuation in only two cases.
CLINICAL IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Melissa Uil, Chi M. Hau, Mohamed Ahdi, James D. Mills, Jesper Kers, Moin A. Saleem, Sandrine Florquin, Victor E. A. Gerdes, Rienk Nieuwland, Joris J. T. H. Roelofs
Summary: This study found that diabetic patients with microalbuminuria and/or macroalbuminuria exhibited increased concentrations of total EVs and EVs from various cell types in the plasma. miR-99a-5p was upregulated in patients with macroalbuminuria and was shown to downregulate mTOR protein expression in cultured human podocytes.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Rheumatology
Zhaomin Mao, Ying Tan, Juan Tao, Linlin Li, Hui Wang, Feng Yu, Andras Perl, Minghui Zhao
Summary: This study evaluated the activation of mammalian target of rapamycin (mTOR) in renal tissue of LN patients. The activation of mTORC1/2 was found to be significantly increased in different cell types of LN patients compared to controls, and mTORC1 activation was strongly associated with clinical and pathological indicators of LN. The study also identified mTORC1 activation as a prognostic marker in LN patients.
Article
Cell Biology
Ya-Chun Han, Shi-Qi Tang, Yu-Ting Liu, Ai-Mei Li, Ming Zhan, Ming Yang, Na Song, Wei Zhang, Xue-Qin Wu, Can-Hui Peng, Hao Zhang, Shikun Yang
Summary: This study investigated the effects of the AMPK agonist metformin on mitophagy and cellular injury in renal tubular cells under diabetic conditions. The results showed that metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice by activating mitophagy through a p-AMPK-Pink1-Parkin pathway. In vitro experiments revealed that metformin promoted mitophagy in HK-2 cells under high glucose/fatty acid conditions by activating AMPK and promoting the translocation of Pink1 to mitochondria.
CELL DEATH & DISEASE
(2021)
Article
Endocrinology & Metabolism
Siddharth Sunilkumar, Esma I. Yerlikaya, Allyson L. Toro, William P. Miller, Han Chen, Kebin Hu, Scot R. Kimball, Michael D. Dennis
Summary: Chronic hyperglycemia promotes the expression of REDD1 in the kidney, leading to oxidative stress and renal injury. Deletion of REDD1 reduces reactive oxygen species and prevents podocyte loss, indicating its role in diabetes-induced renal complications.
Article
Urology & Nephrology
Sameera Gunawardena, Maleesha Dayaratne, Harshima Wijesinghe, Eranga Wijewickrama
Summary: Thirteen studies were included in the scoping review. Interstitial fibrosis was the predominant lesion in all studies. Although no characteristic histopathological feature could be found in CKDu-Sri Lanka or Mesoamerican nephropathy, there are noticeable differences between these two groups in the frequency and severity of the glomerular and tubulointerstitial changes.
KIDNEY INTERNATIONAL REPORTS
(2021)
Article
Endocrinology & Metabolism
Jinjin Li, Guangjie Liu, Qiumei Zhang, Rongna Dong, Jingyun Zhang
Summary: Diabetic kidney disease (DKD) is a microvascular complication of poorly controlled diabetes caused by chronic hyperglycemia. Metformin, a first-line drug in oral treatment of type 2 diabetes mellitus, has been found to have a protective effect on DKD. This study aimed to investigate the regulatory role of metformin in DKD.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Medicine, General & Internal
Francesca Lanzaro, Annalisa Barlaba, Angelica De Nigris, Federica Di Domenico, Valentina Verde, Emanuele Miraglia del Giudice, Anna Di Sessa
Summary: Diabetic nephropathy (DN) is the most common microvascular complication in patients with diabetes. Novel potential biomarkers, such as microRNAs (miRNAs), have been proposed to improve early identification of DN. These regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Charlotte Delrue, Reinhart Speeckaert, Joris R. Delanghe, Marijn M. Speeckaert
Summary: Vitamin D may play a significant role in the development of diabetic nephropathy, but its influence on the reversal of existing renal damage remains uncertain. Several hypotheses suggest a link between vitamin D and inflammation, oxidative stress, and extracellular matrix accumulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)