title: Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy.
abstract: Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Mengying
authors: M
authors: Zhou
authors: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, No. 457 Zhongshan Road, Dalian 116023, China.
authors: Xulang
authors: X
authors: Zhang
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Xinyu
authors: X
authors: Wen
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Taihua
authors: T
authors: Wu
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Weidong
authors: W
authors: Wang
authors: Department of Urology, Dalian Friendship Hospital, No. 8 Sanba Square, Dalian, 116001, China.
authors: Mingzhou
authors: M
authors: Yang
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Jing
authors: J
authors: Wang
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Ming
authors: M
authors: Fang
authors: Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, No. 457 Zhongshan Road, Dalian 116023, China.
authors: Bingcheng
authors: B
authors: Lin
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Hongli
authors: H
authors: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D056656:Lab-On-A-Chip Devices; D009393:Nephritis / Q000503:physiopathology*; D050199:Podocytes / Q000166:cytology; D051381:Rats; D011918:Rats, Inbred SHR; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D000199:Actins; D007074:Immunoglobulin G; D001613:beta 2-Microglobulin