Review
Cell Biology
Jiao-Yi Chen, Wai-Han Yiu, Patrick Ming-Kuen Tang, Sydney Chi-Wai Tang
Summary: Fibrotic signaling plays a crucial role in the development and progression of renal cell carcinoma. Targeting classic fibrotic signaling processes such as TGF-beta signaling and EMT shows promising antitumor effects both preclinically and clinically. A better understanding of the molecular mechanisms of fibrotic signaling in renal cell carcinoma can facilitate the development of precision therapies against solid cancers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Yan Lin, Fangfang Cai, Xiaoyang Wang, Yunwen Yang, Yongzhe Ren, Chun Yao, Xiaoxing Yin, Hongqin Zhuang, Zichun Hua
Summary: This study suggests that FADD may play a critical role in the development of renal fibrosis. Through various staining and immunofluorescence analysis, neutrophil infiltration, glomerular mesangial cell proliferation, and base-membrane thickening were observed in FADD-D mice. Macrophage infiltration was significantly enhanced, and the levels of renal fibrosis-related markers were elevated. Mechanism study indicates that FADD phosphorylation may activate the TLR4/myD88/NF-kappa B signaling pathway as well as the mTOR and TGF-beta/Smad pathway, accelerating the process of epithelial mesenchymal transition and eventually resulting in IgA nephritis and renal fibrosis.
Article
Immunology
Min Yang, Jia Wei Liu, Yu Ting Zhang, Gang Wu
Summary: M2 macrophages, AIM and TGF-beta 1 play important roles in the progression of IgAN fibrosis, and they are interrelated. Their expression levels are positively correlated with serum creatinine, 24-hour proteinuria, and fibrotic area, while negatively correlated with eGFR.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Seong-Hye Hwang, Yun-Mi Lee, Yunyeong Choi, Hyung Eun Son, Ji Young Ryu, Ki Young Na, Ho Jun Chin, Noo Li Jeon, Sejoong Kim
Summary: This study developed fibrosis-mimicking models using 3D co-culture devices to evaluate the effects of TGF-beta and TGF-beta inhibitor treatment on renal fibrosis. The expression of fibrosis marker in cells increased upon TGF-beta treatment, while vessel density in the vascular compartment varied with TGF-beta and TGF-beta inhibitor treatment. Multiplex ELISA analysis showed increased levels of inflammatory cytokines and growth factors in the TGF-beta-stimulating 3D models, mimicking the fibrotic microenvironments of human kidneys. This study may lead to the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tessa Gerrits, Isabella J. Brouwer, Kyra L. Dijkstra, Ron Wolterbeek, Jan A. Bruijn, Marion Scharpfenecker, Hans J. Baelde
Summary: Chronic kidney disease (CKD) involves progressive deterioration of renal function, characterized by glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Endoglin, expressed in endothelial cells and fibroblasts, may function as a co-receptor of TGF signaling and potentially play a role in the progression of CKD. The study found that endoglin was upregulated in patients with CKD, particularly those with chronic allograft dysfunction and diabetic nephropathy. The overexpression of endoglin in human kidney fibroblasts also resulted in increased mRNA and protein upregulation of ECM components, suggesting its significance as a therapeutic target for the prevention of end-stage renal disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Yuzhan Zhang, Ke Li, Yan Li, Weihao Zhao, Li Wang, Zhao Chen, Xiaotao Ma, Tian Yao, Jinhua Wang, Wei Dong, Xiancheng Li, Xuefei Tian, Rongguo Fu
Summary: This study found increased expression of DPP8 and DPP9 in renal proximal tubule epithelial cells of CKD patients, and using a DPP8/DPP9 inhibitor significantly attenuated tubulointerstitial injury and improved renal function.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Ji-chao Wu, Xiao-jie Wang, Jing-han Zhu, Xue-ying Huang, Min Liu, Zhe Qiao, Yan Zhang, Yu Sun, Zi-ying Wang, Peng Zhan, Tao Zhang, Hui-li Hu, Hong Liu, Wei Tang, Fan Yi
Summary: This study found that GPR97 is significantly upregulated in hypertensive nephropathy and is involved in the development of tubulointerstitial fibrosis. GPR97(-/-) mice showed elevated blood pressure but reduced renal injury and fibrosis. Knockdown of GPR97 in cells inhibited TGF-beta signaling by disrupting RhoA-mediated cytoskeletal reorganization and clathrin-mediated endocytosis of TGF-beta receptors.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Pharmacology & Pharmacy
Xiao-Long Li, Jing Liu, Xiao-Shan Chen, Li-Min Cheng, Wei-Ling Liu, Xing-Feng Chen, Yue-Jiao Li, Yong-Yuan Guan, Xin Zeng, Yan-Hua Du
Summary: The study found that TMEM16A is involved in the progression of renal fibrosis, and blocking TMEM16A can prevent the development of kidney fibrosis. This discovery may be a new target for the treatment of renal fibrosis.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Cell Biology
Yuqing Zhang, De Jin, Xiaomin Kang, Rongrong Zhou, Yuting Sun, Fengmei Lian, Xiaolin Tong
Summary: The review discusses the pathological mechanisms of diabetic renal fibrosis and related signaling pathways to provide novel therapeutic intervention insights for clinical research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Orthopedics
Rahul G. Alenchery, Raquel E. Ajalik, Kyle Jerreld, Firaol Midekksa, Sylvia Zhong, Bashar Alkatib, Hani A. Awad
Summary: This study found that transforming growth factor-beta (TGF-beta 1) induces plasminogen activator inhibitor 1 (PAI-1) to inhibit phosphatase and tensin homolog (PTEN), suggesting that PAI-1-induced adhesions involve phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling. PAI-1 deletion blunted TGF-beta 1-induced myofibroblast activation in murine flexor tenocytes and increased the gene expression of Mmp-2 to confer protective effects against fibrosis. While TGF-beta 1 significantly reduced phosphorylation of PTEN in WT cells, PAI-1 deletion rescued the activation of PTEN.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Plant Sciences
Zhenyu Liu, Weili Wang, Xueqin Li, Sha Tang, Dongwei Meng, Wenli Xia, Hong Wang, Yuzhang Wu, Xinyuan Zhou, Jingbo Zhang
Summary: Capsaicin can effectively alleviate renal fibrosis, possibly by suppressing the activation of myofibroblasts and protecting against the phenotypic alteration of tubular epithelial cells. This is mainly achieved through the inhibition of the TGF-beta 1-Smad2/3 signaling pathway.
Article
Chemistry, Multidisciplinary
Lihua Luo, Sijie Wang, Yilong Hu, Litong Wang, Xindong Jiang, Junlei Zhang, Xu Liu, Xuemeng Guo, Zhenyu Luo, Chunqi Zhu, Miaomiao Xie, Yeqing Li, Jian You, Fuchun Yang
Summary: Macrophages play a central role in kidney disease and can either promote tissue repair or drive tissue fibrosis depending on their polarization. This study identified M2a-derived macrophage-to-myofibroblast transition (MMT) cells as responsible for renal fibrosis development and demonstrated that TGF-beta signaling intensity is a major factor determining the differential polarization of M2a and M2c. By using targeted nanotechnology, the study showed that modulating the ATF6/TGF-beta/Smad3 signaling axis within macrophages can promote the polarization of M2c phenotype and suppress excessive MMT polarization, offering a potential therapeutic approach for renal fibrosis.
Article
Cell Biology
Shu Yang, Guangyan Yang, Xinyu Wang, Jiaqing Xiang, Lin Kang, Zhen Liang
Summary: This study demonstrates the anti-fibrotic role of SIRT2 in renal tubules and hepatocytes. SIRT2 inhibits fibrotic gene expression by reducing the activation of the TGF-beta signaling pathway. It interacts with and deacetylates SMAD2 and SMAD3 to promote their degradation and decrease the activation of SMAD3.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Liangmei Chen, Xiaofan Li, Yiyao Deng, Jianwen Chen, Mengjie Huang, Fengge Zhu, Zhumei Gao, Lingling Wu, Quan Hong, Zhe Feng, Guangyan Cai, Xuefeng Sun, Xueyuan Bai, Xiangmei Chen
Summary: This study found that the transformation of cells into myofibroblasts during renal injury is a common phenomenon and the process is associated with cellular respiration, regulated by TGF-beta 1. By inhibiting the production of cellular respiration, the occurrence of cell transformation can be slowed down.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Qixia Liu, Xiaohui Chen, Min Kan, Jing Yang, Qian Gong, Rui Jin, Yulong Dai, Juan Jin, Hongmei Zang
Summary: The study investigated the therapeutic effect and mechanism of the Chinese medicine monomer Gypenoside XLIX on renal fibrosis, as well as the targeting and therapeutic effects of PLGA-Gyp XLIX nanoparticles in UUO kidney. The results showed that PLGA-Gyp XLIX nanoparticles could effectively inhibit renal fibrosis, reduce collagen deposition and renal tubular necrosis. This study opens up a promising pathway for targeted drug treatment of renal fibrosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Endocrinology & Metabolism
Marco Gallo, Giouanna Muscogiuri, Francesco Felicetti, Antongiulio Faggiano, Francesco Trimarchi, Emanuela Arvat, Riccardo Vigneri, Annamaria Colao
METABOLISM-CLINICAL AND EXPERIMENTAL
(2018)
Editorial Material
Medicine, General & Internal
Kristin D'Silva, Sarah Brown, Gary M. Hunninghake, Marina Vivero, Joseph Loscalzo
NEW ENGLAND JOURNAL OF MEDICINE
(2019)
Article
Rheumatology
Cianna Leatherwood, Cameron B. Speyer, Candace H. Feldman, Kristin D'Silva, Jose A. Gomez-Puerta, Paul J. Hoover, Sushrut S. Waikar, Gearoid M. McMahon, Helmut G. Rennke, Karen H. Costenbader
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2019)
Editorial Material
Medicine, General & Internal
Caren G. Solomon
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Article
Rheumatology
Chio Yokose, April Jorge, Kristin D'Silva, Naomi Serling-Boyd, Mark Matza, Mazen Nasrallah, Sarah Keller, Amar Oza, Hyon Choi, Marcy B. Bolster, Deborah Collier
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2020)
Article
Rheumatology
Jacob J. E. Koopman, Helmut G. Rennke, Cianna Leatherwood, Cameron B. Speyer, Kristin D'Silva, Gearoid M. McMahon, Sushrut S. Waikar, Karen H. Costenbader
Article
Rheumatology
Kristin M. D'Silva, Chio Yokose, Na Lu, Natalie McCormick, Hwajeong Lee, Yuqing Zhang, Hyon K. Choi
Summary: The study found no long-term excess mortality risk among American women with SU levels as low as <3 mg/dl, but observed a 28% higher mortality risk in men with SU levels <4 mg/dl. This suggests a potential causal relationship between hypouricemia and mortality in men, particularly from diabetes mellitus.
ARTHRITIS CARE & RESEARCH
(2021)
Article
Rheumatology
Kristin M. D'Silva, April Jorge, Andrew Cohen, Natalie McCormick, Yuqing Zhang, Zachary S. Wallace, Hyon K. Choi
Summary: The study found that COVID-19 patients with systemic autoimmune rheumatic diseases may have a higher risk of hospitalization, ICU admission, acute renal failure, and venous thromboembolism compared to those without systemic ARDs. These risks may be largely influenced by comorbidities, except for the risk of venous thromboembolism.
ARTHRITIS & RHEUMATOLOGY
(2021)
Article
Oncology
Ioana A. Dobre, Angela J. Frank, Kristin M. D'Silva, David C. Christiani, Daniel Okin, Amita Sharma, Sydney B. Montesi
Summary: This study found that patients with ILD receiving PD-1 inhibitors more frequently died from cancer-related causes than from ILD. Further research is needed to determine the safety of ICIs in patients with ILD and if ILD subtype may help to refine ICI-associated risks.
CLINICAL LUNG CANCER
(2021)
Article
Rheumatology
Kristin M. D'Silva, Zachary S. Wallace
Summary: Baseline glucocorticoid use is associated with severe COVID-19 outcomes in autoimmune disease patients, but DMARDs categories do not appear to increase risk. Randomized clinical trials show glucocorticoids reduce mortality in severe COVID-19, while other agents like baricitinib may improve outcomes in certain populations. More research is needed to guide DMARD management in autoimmune disease patients during the pandemic and their role in COVID-19 treatment.
CURRENT RHEUMATOLOGY REPORTS
(2021)
Article
Health Care Sciences & Services
Sara Jane Cromer, Kristin M. D'Silva, Elaine W. Yu, Joan Landon, Rishi J. Desai, Seoyoung C. Kim
Summary: The study found that the use of denosumab has surpassed all other bone-directed therapies over the past decade, especially since its approval in 2010. The use of denosumab also showed increasing trends among patients with osteoporosis, malignancies, and recent fractures. However, it is noteworthy that the proportion of using any bone-directed therapy after fractures is low and has declined over time.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2022)
Article
Rheumatology
Kristin M. D'Silva, Iazsmin Bauer Ventura, Marcy B. Bolster, Flavia Castelino, Amita Sharma, Brent P. Little, Ayodeji Adegunsoye, Mary E. Strek, Hyon Choi, Sydney B. Montesi
Summary: A multicentre observational study examined the use of rituximab (RTX) in interstitial pneumonia with autoimmune features (IPAF) patients. The majority of IPAF patients treated with RTX at two medical centres demonstrated improvement or stability at 1 year, calling for prospective studies to determine the risks, benefits and cost effectiveness of RTX in IPAF.
RHEUMATOLOGY ADVANCES IN PRACTICE
(2021)
Article
Respiratory System
A. Sclafani, K. M. D'Silva, B. P. Little, E. M. Miloslavsky, J. J. Locascio, A. Sharma, S. B. Montesi
RESPIRATORY RESEARCH
(2019)
Review
Food Science & Technology
Giovanna Muscogiuri, Giancarlo Balercia, Luigi Barrea, Angelo Cignarelli, Francesco Giorgino, Jens J. Holst, Daniela Laudisio, Francesco Orio, Giacomo Tirabassi, Annamaria Colao
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2018)
Article
Endocrinology & Metabolism
Rosario Pivonello, Giovanna Muscogiuri, Geoffrey Holder, Michaela Paul, Severine Sarp, Anastasia Lesogor, Pierre Jordaan, Johannes Eisinger, Annamaria Colao