Review
Biochemistry & Molecular Biology
Alison Domingues, Alessandro Fantin
Summary: The vascular endothelium acts as a selective barrier to regulate macromolecule exchange, but its integrity is compromised in various pathological conditions, leading to increased vascular hyperpermeability. VEGFA is a potent permeability factor, and NRP1 may play a fundamental role in regulating VEGFA-induced responses in vascular endothelial cells.
Article
Cell Biology
Rimar Doron, Lidar Merav, Eiza Nasrin, Sabag D. Adi, Toubi Elias, Slobodin Gleb, Rosner Itzhak, Rozenbaum Michael, Vadasz Zahava
Summary: The study showed that urine concentrations of Sema3A were significantly lower in SLE patients, especially those with renal involvement. Urine Sema3A levels were inversely correlated with proteinuria and SLE disease activity, suggesting it could be a potential biomarker for disease activity and renal involvement in lupus patients.
Article
Neurosciences
Luis F. Martins, Ilaria Brambilla, Alessia Motta, Stefano de Pretis, Ganesh Parameshwar Bhat, Aurora Badaloni, Chiara Malpighi, Neal D. Amin, Fumiyasu Imai, Ramiro D. Almeida, Yutaka Yoshida, Samuel L. Pfaff, Dario Bonanomi
Summary: The close apposition of neurons and endothelial cells is crucial for the function of the nervous system. Motor neurons release a signaling molecule called Sema3C to repel endothelial cells and promote axon growth. The Plexin-D1 receptor in endothelial cells is found to be necessary for the development of neuromuscular connectivity. This study provides insights into the mechanisms that enable the avoidance of detrimental axon-endothelial encounters and facilitate vascularization within the nervous system.
Article
Biochemistry & Molecular Biology
Sabine Stoeckl, Johanna Reichart, Magdalena Zborilova, Brian Johnstone, Susanne Graessel
Summary: Osteoarthritis (OA) is a complex disorder characterized by articular cartilage destruction and changes in other articular tissues. Recent research has shown that Semaphorin 3A (Sema3A) plays a role in the pathophysiology of cartilage OA. This study reveals that the Sema3A-Nrp-1 signaling axis can affect the metabolism and viability of OA chondrocytes by inducing MMP13 expression and compromising pro-survival AKT activation. Targeting this signaling pathway might be a potential opportunity for intervening in the pathogenesis and progression of OA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Bo Jiao, Shiyang Liu, Xi Tan, Pei Lu, Danning Wang, Hui Xu
Summary: Semaphorins, particularly Class-3 Semaphorins (SEMA3), have broad influences on pathophysiological processes such as bone remodeling, immune responses, and angiogenesis. While angiogenesis plays a crucial role in many diseases, targeting it for therapy has been challenging due to its complex mechanisms. Investigating the specific mechanisms of SEMA3 in angiogenesis may lead to novel therapeutic approaches for diseases.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Immunology
Shreya M. Kanth, Salina Gairhe, Parizad Torabi-Parizi
Summary: Semaphorins are a group of proteins that play a critical role in neuronal development and have effects on tumors, autoimmune diseases, and immune responses. Recent literature has highlighted their regulatory role in innate immunity and diseases caused by acute injuries, such as in the kidneys, abdomen, heart, and lungs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Junnan Xu, Xiubin Li, Qing Yuan, Chenfeng Wang, Liang Xu, Xing Wei, Haitao Liu, Bo Yu, Zhekun An, Yuanyu Zhao, Xiang Li, Xu Zhang, Xin Ma, Ming Cai
Summary: The study demonstrates that Sema4A can alleviate kidney ischemia reperfusion injury by enhancing the stability and function of Treg cells, reducing neutrophil and proinflammatory macrophage accumulation.
KIDNEY INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Zheng Yin, Jishou Zhang, Shuwan Xu, Jianfang Liu, Yao Xu, Junping Yu, Mengmeng Zhao, Wei Pan, Menglong Wang, Jun Wan
Summary: This review summarizes the role of Semaphorins and their receptors in the pathological progression of cardiovascular diseases, highlighting their potential as therapeutic targets and novel biomarkers for these diseases.
Article
Cell Biology
Simon Bernatz, Daniel Monden, Florian Gessler, Tijana Radic, Elke Hattingen, Christian Senft, Volker Seifert, Michael W. Ronellenfitsch, Karl H. Plate, Patrick N. Harter, Peter Baumgarten
Summary: The study found significantly increased levels of VEGF-A in WHO grade III meningiomas, with positive correlations with expression of VEGFR-1 and VEGFR-3. VEGFR-2 expression was positively associated with progression-free survival. VEGF-A on tumor cells was negatively correlated with overall survival.
JOURNAL OF MOLECULAR HISTOLOGY
(2021)
Review
Medicine, Research & Experimental
Roberta Mastrantonio, Hua You, Luca Tamagnone
Summary: Semaphorins play a crucial role in cancer by controlling various biological processes, especially in cell-cell communication, migration, metastasis, and immune responses. Research suggests that Semaphorins could serve as important biomarkers for predicting patient survival and treatment response in cancer. Targeting Semaphorin signaling has shown potential in interfering with tumor growth and metastasis, making it a promising avenue for novel therapeutic strategies in cancer treatment.
Article
Urology & Nephrology
Anxiang Cai, Guanyu Ye, Sandrine Placier, Perrine Frere, Brigitte Surin, Sophie Vandermeersch, Raphael Kormann, Yi-Chun Xu-Dubois, Magali Genest, Morgane Lannoy, Christos E. Chadjichristos, Jean-Claude Dussaule, Peter J. Scambler, Christos Chatziantoniou, Amelie Calmont
Summary: The study highlights the important role of endothelial dysfunction in acute kidney injury and identifies SEMA3C as a key factor associated with this condition. Experimental findings demonstrate that SEMA3C promotes interstitial edema, leucocyte infiltration, and tubular injury, and also reveals a novel role for SEMA3C in promoting vascular permeability. These findings suggest that SEMA3C could be a potential therapeutic target for acute kidney injury.
KIDNEY INTERNATIONAL
(2022)
Article
Anesthesiology
Harrison J. Stratton, Lisa Boinon, Kimberly Gomez, Laurent Martin, Paz Duran, Dongzhi Ran, Yuan Zhou, Shizhen Luo, Samantha Perez-Miller, Marcel Patek, Mohab M. Ibrahim, Amol Patwardhan, Aubin Moutal, Rajesh Khanna
Summary: Blocking the interaction between neuropilin 1 (NRP1) and vascular endothelial growth factor A (VEGF-A) can alleviate neuronal sensitization and pain in chronic neuropathic pain models. In an in-silico screening, a small molecule named NRP1-4 was identified to inhibit the effects of VEGF-A on sensory neurons. Treatment with NRP1-4 significantly attenuated mechanical allodynia and thermal hyperalgesia in animal models of neuropathic pain.
Article
Urology & Nephrology
Isabelle Ayoub, Bethany J. Wolf, Linyu Geng, Huijuan Song, Aastha Khatiwada, Betty P. Tsao, Jim C. Oates, Brad H. Rovin
Summary: A machine learning approach combining traditional clinical data and novel urine biomarkers was used to develop prediction models for one-year treatment response in lupus nephritis. The models showed good predictive value, with the best performance seen in predicting eGFR response. The inclusion of both traditional clinical data and novel urine biomarkers, including cytokines, chemokines, and markers of kidney damage, was found to improve the prediction accuracy.
KIDNEY INTERNATIONAL
(2022)
Article
Immunology
Shannon N. Loftus, Jianhua Liu, Celine C. Berthier, Johann E. Gudjonsson, Mehrnaz Gharaee-Kermani, Lam C. Tsoi, J. Michelle Kahlenberg
Summary: Abnormal activation of the immune system is a known cause of lupus. Inhibiting the inflammasome and its downstream components has been shown to reduce disease severity in lupus mouse models. This study examines the effects of IL-1 beta loss on disease severity in a lupus-prone mouse model and identifies potential clinical relevance of TNF and IL-17 signaling pathways. Caution may be needed when inhibiting inflammasome or IL-1 beta signaling in SLE, especially in patients with renal involvement.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Yu-Hsuan Hung, Ya-Chin Hou, Shih-Han Hsu, Li-Yun Wang, Ya-Li Tsai, Yan-Shen Shan, Yung-Yeh Su, Wen-Chun Hung, Li-Tzong Chen
Summary: Perineural invasion and neurogenesis are common in pancreatic ductal adenocarcinoma (PDAC), and upregulated expression of semaphorin 3A (SEMA3A) is observed in PDAC. This study found that cancer-secreted SEMA3A promotes neural migration, neurite outgrowth, and neural recruitment, and these effects are dependent on the activation of receptors PLXNA1, NRP2, and MAPK. Inhibition of SEMA3A can reduce neural recruitment, tumor growth, and dissemination in PDAC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)