한빛사논문
- 조회934
Joon Ho Kang,1* Minjeong Jang1, Su Jin Seo1,2, Andrew Choi1, Daeeun Shin1,3, Suyoung Seo1,4, Soo Hyun Lee,1,5* and Hong Nam Kim1,5,6,7*
1Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
2Department of Chemical Engineering, Kwangwoon University, Seoul 01897, Republic of Korea
3School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
4Program in Nano Science and Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
5Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea
6School of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea
7Yonsei-KIST Convergence Research Institute, Yonsei University, Seoul 03722, Republic of Korea
CORRESPONDING AUTHORS: Joon Ho Kang, Soo Hyun Lee, Hong Nam Kim
Abstract
In infectious disease such as sepsis and COVID-19, blood vessel leakage treatment is critical to prevent fatal progression into multi-organ failure and ultimately death, but the existing effective therapeutic modalities that improve vascular barrier function are limited. Here, this study reports that osmolarity modulation can significantly improve vascular barrier function, even in an inflammatory condition. 3D human vascular microphysiological systems and automated permeability quantification processes for high-throughput analysis of vascular barrier function are utilized. Vascular barrier function is enhanced by >7-folds with 24–48 h hyperosmotic exposure (time window of emergency care; >500 mOsm L−1) but is disrupted after hypo-osmotic exposure (<200 mOsm L−1). By integrating genetic and protein level analysis, it is shown that hyperosmolarity upregulates vascular endothelial-cadherin, cortical F-actin, and cell–cell junction tension, indicating that hyperosmotic adaptation mechanically stabilizes the vascular barrier. Importantly, improved vascular barrier function following hyperosmotic exposure is maintained even after chronic exposure to proinflammatory cytokines and iso-osmotic recovery via Yes-associated protein signaling pathways. This study suggests that osmolarity modulation may be a unique therapeutic strategy to proactively prevent infectious disease progression into severe stages via vascular barrier function protection.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-02-21)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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