MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2
Abstract Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve r...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-01-01
|
| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01373-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825197666834841600 |
|---|---|
| author | Fang-Yuan Liu Young-Lai Cho Fitri Rahma Fridayana Lashkari Niloofar Minh Nhat Vo Yan Huang Anita Limanjaya Mi-Hye Kwon Jiyeon Ock Seon-Jin Lee Guo Nan Yin Nam-Kyung Lee Ji-Kan Ryu |
| author_facet | Fang-Yuan Liu Young-Lai Cho Fitri Rahma Fridayana Lashkari Niloofar Minh Nhat Vo Yan Huang Anita Limanjaya Mi-Hye Kwon Jiyeon Ock Seon-Jin Lee Guo Nan Yin Nam-Kyung Lee Ji-Kan Ryu |
| author_sort | Fang-Yuan Liu |
| collection | DOAJ |
| description | Abstract Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, strategies for activating the Tie2 signaling pathway have been developed as potential therapies for neurovascular diseases. Here, we developed a human Tie2-agonistic antibody (MT-100) that not only resists Ang-2 antagonism and activates Tie2 signaling but also regulates a novel target, sushi repeat-containing protein X-linked 2 (Srpx2). This regulation led to the survival of vascular and neuronal cells, a reduction in the production of reactive oxygen species (ROS), activation of the PI3K/AKT/eNOS signaling pathway, increased expression of neurotrophic factors, and ultimately alleviation of ED in diabetic mice. Our findings not only provide conclusive evidence that MT-100 is a promising therapeutic strategy for the treatment of diabetic ED but also suggest it has substantial clinical applications for other complications associated with diabetes. |
| format | Article |
| id | doaj-art-bfa5fd71be13406db35a73aacd87c77e |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-bfa5fd71be13406db35a73aacd87c77e2025-02-09T12:14:10ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-01-0157110411710.1038/s12276-024-01373-1MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2Fang-Yuan Liu0Young-Lai Cho1Fitri Rahma Fridayana2Lashkari Niloofar3Minh Nhat Vo4Yan Huang5Anita Limanjaya6Mi-Hye Kwon7Jiyeon Ock8Seon-Jin Lee9Guo Nan Yin10Nam-Kyung Lee11Ji-Kan Ryu12National Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineEnvironmental Disease Research Center, Korea Research Institute of Bioscience and BiotechnologyNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineEnvironmental Disease Research Center, Korea Research Institute of Bioscience and BiotechnologyNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineBiotherapeutics Translational Research Center, Korea Research Institute of Bioscience and BiotechnologyNational Research Center for Sexual Medicine and Department of Urology, Inha University College of MedicineAbstract Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, strategies for activating the Tie2 signaling pathway have been developed as potential therapies for neurovascular diseases. Here, we developed a human Tie2-agonistic antibody (MT-100) that not only resists Ang-2 antagonism and activates Tie2 signaling but also regulates a novel target, sushi repeat-containing protein X-linked 2 (Srpx2). This regulation led to the survival of vascular and neuronal cells, a reduction in the production of reactive oxygen species (ROS), activation of the PI3K/AKT/eNOS signaling pathway, increased expression of neurotrophic factors, and ultimately alleviation of ED in diabetic mice. Our findings not only provide conclusive evidence that MT-100 is a promising therapeutic strategy for the treatment of diabetic ED but also suggest it has substantial clinical applications for other complications associated with diabetes.https://doi.org/10.1038/s12276-024-01373-1 |
| spellingShingle | Fang-Yuan Liu Young-Lai Cho Fitri Rahma Fridayana Lashkari Niloofar Minh Nhat Vo Yan Huang Anita Limanjaya Mi-Hye Kwon Jiyeon Ock Seon-Jin Lee Guo Nan Yin Nam-Kyung Lee Ji-Kan Ryu MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 Experimental and Molecular Medicine |
| title | MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 |
| title_full | MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 |
| title_fullStr | MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 |
| title_full_unstemmed | MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 |
| title_short | MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2 |
| title_sort | mt 100 a human tie2 agonistic antibody improves penile neurovasculature in diabetic mice via the novel target srpx2 |
| url | https://doi.org/10.1038/s12276-024-01373-1 |
| work_keys_str_mv | AT fangyuanliu mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT younglaicho mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT fitrirahmafridayana mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT lashkariniloofar mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT minhnhatvo mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT yanhuang mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT anitalimanjaya mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT mihyekwon mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT jiyeonock mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT seonjinlee mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT guonanyin mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT namkyunglee mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 AT jikanryu mt100ahumantie2agonisticantibodyimprovespenileneurovasculatureindiabeticmiceviathenoveltargetsrpx2 |