Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease-Reference-Cited by-同舟云学术

Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease

Published:2022-11-04 Issue:12 Volume:71 Page:2664-2676
ISSN:0012-1797
Container-title:Diabetes
language:en
Short-container-title:

Author:

Liu Jiahao¹²,Nair Viji¹,Zhao Yi-yang³,Chang Dong-yuan³,Limonte Christine⁴,Bansal Nisha⁴,Fermin Damian¹,Eichinger Felix¹,Tanner Emily C.¹,Bellovich Keith A.⁵,Steigerwalt Susan⁶,Bhat Zeenat⁷,Hawkins Jennifer J.¹,Subramanian Lalita¹,Rosas Sylvia E.⁸,Sedor John R.⁹,Vasquez Miguel A.¹⁰,Waikar Sushrut S.¹¹,Bitzer Markus¹,Pennathur Subramaniam¹,Brosius Frank C.¹¹²,De Boer Ian⁴,Chen Min³,Kretzler Matthias¹¹³,Ju Wenjun¹¹³^ORCID,Knight Richard,Lecker Stewart H.,Stillman Isaac,Bogen Steve,Amodu Afolarin A.,Ilori Titlayo,Maikhor Shana,Schmidt Insa,Beck Laurence H.,Henderson Joel M.,Onul Ingrid,Verma Ashish,Waikar Sushrut,McMahon Gearoid M.,Valerius M. Todd,Waikar Sushrut,Weins Astrid,Colona Mia R.,Greka Anna,Hacohen Nir,Hoover Paul J.,Marshall Jamie L.,Aulisio Mark,Chen Yijiang M.,Janowczyk Andrew,Jayapandian Catherine,Viswanathan Vidya S.,Bush William S.,Crawford Dana C.,Madabhushi Anant,Bush Lakeshia,Cooperman Leslie,Gonzalez-Vicente Agustin,Herlitz Leal,Jolly Stacey,Nguyen Jane,O’toole John,Palmer Ellen,Poggio Emilio,Sedor John,Sendrey Dianna,Spates-Harden Kassandra,Taliercio Jonathan,Bjornstad Petter M.,Pyle Laura,Vinovskis Carissa,Appelbaum Paul,Barasch Jonathan M.,Bomback Andrew S.,Canetta Pietro A.,D’Agati Vivette D.,Kiryluk Krzysztof,Kudose Satoru,Mehl Karla,Shang Ning,Balderes Olivia,Bansal Shweta,Alexandrov Theodore,Rennke Helmut,El-Achkar Tarek M.,Barwinska Daria,Bledsoe Sharon,Borner Katy,Bueckle Andreas,Cheng Yinghua,Dagher Pierre C.,Dunn Kenneth W.,Eadon Michael T.,Ferkowicz Michael J.,Herr Bruce W.,Kelly Katherine J.,Melo Ferreira Ricardo,Quardokus Ellen M.,Record Elizabeth,Rivera Marcelino,Su Jing,Sutton Timothy A.,Williams James C.,Winfree Seth,Menez Steven,Parikh Chirag R.,Rosenberg Avi,Corona-Villalobos Celia P.,Wen Yumeng,Johansen Camille,Rosas Sylvia E.,Roy Neil,Sun Jennifer,Williams Mark,Azeloglu Evren U.,Hansen Jens,He Cijang,Iyengar Ravi,Xiong Yuguang,Prasad Pottumarthi,Srivastava Anand,Madhavan Sethu M.,Parikh Samir,Rovin Brad,Shapiro John P.,Anderton Christopher R.,Lukowski Jessica,Pasa-Tolic Ljiljana,Velickovic Dusan,Oliver George (Holt),Ardayfio Joseph,Bebiak Jack,Brown Keith,Campbell Taneisha,Campbell Catherine E.,Hayashi Lynda,Jefferson Nichole,Roberts Glenda V.,Saul John,Shpigel Anna,Stutzke Christy,Koewler Robert,Pinkeney Roy,Sealfon Rachel,Troyanskaya Olga,Wong Aaron,Tuttle Katherine R.,Pollack Ari,Goltsev Yury,Lucarelli Nicholas,Sarder Pinaki,Lake Blue B.,Zhang Kun,Boada Patrick,Laszik Zoltan G.,Nolan Garry,Anjani Kavya,Sarwal Minnie,Mukatash Tariq,Sigdel Tara,Alloway Rita R.,Burg Ashley R.,Lee Paul J.,Rike Adele,Shi Tiffany,Woodle E. Steve,Balis Ulysses G.J.,Blanc Victoria M.,Conser Ninive C.,Eddy Sean,Frey Renee,He Yougqun,Hodgin Jeffrey B.,Kretzler Matthias,Lienczewski Chrysta,Luo Jinghui,Mariani Laura H.,Menon Rajasree,Otto Edgar,Schaub Jennifer,Steck Becky,Elder Michele M.,Gilliam Matthew,Hall Daniel E.,Murugan Raghavan,Palevsky Paul M.,Randhawa Parmjeet,Rosengart Matthew,Tublin Mitchell,Vita Tina,Kellum John A.,Winters James,Alpers Charles E.,Berglund Ashley,Blank Kristina N.,Carson Jonas,Daniel Stephen,De Boer Ian H.,Dighe Ashveena L.,Dowd Frederick,Grewenow Stephanie M.,Himmelfarb Jonathan,Hoofnagle Andrew N.,Limonte Christine,McClelland Robyn L.,Mooney Sean D.,Rezaei Kasra,Shankland Stuart,Snyder Jamie,Wang Ruikang,Wilcox Adam,Williams Kayleen,Park Christopher,Bansal Shweta,Montellano Richard,Pamreddy Annapurna,Sharma Kumar,Venkatachalam Manjeri,Ye Hongping,Zhang Guanshi,Hedayati S. Susan,Kermani Asra,Lee Simon C.,Lu Christopher Y.,Miller R. Tyler,Moe Orson W.,Patel Jiten,Pillai Anil,Sambandam Kamalanathan,Torrealba Jose,Toto Robert D.,Vazquez Miguel,Wang Nancy,Wen Natasha,Zhang Dianbo,Park Harold,Caprioli Richard M.,Patterson Nathan,Sharman Kavya,Spraggins Jeffrey M.,Van de Plas Raf,Basta Jeanine,Diettman Sabine M.,Gaut Joseph P.,Jain Sanjay,Rauchman Michael I.,Vijayan Anitha,Cantley Lloyd G.,Kakade Vijaykumar R.,Moledina Dennis,Shaw Melissa M.,Ugwuowo Ugochukwu,Wilson Francis P.,Arora Tanima,Bitzer Markus,Brosius Frank C.,Gadegbeku Crystal,Gipson Debbie,Hawkins Jennifer,Kretzler Matthias,Lienczewski Chrysta,Pennathur Subramaniam,Troost Jonathan,Gadegbeku Crystal,Bellovich Keith,Bhat Zeenat,Massengill Susan,Perumal Kalyani, ,

Affiliation:

1. 1Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

2. 2Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, China

3. 3Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China

4. 4Division of Nephrology, University of Washington, Seattle, WA

5. 5Nephrology, Ascension St. John Hospital, Detroit, MI

6. 6Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

7. 7Department of Nephrology and Hypertension, Department of Medicine, Wayne State University, Detroit, MI

8. 8Kidney and Hypertension Unit, Joslin Diabetes Center and Harvard Medical School, Boston, MA

9. 9Department of Medicine, Cleveland Clinic, Cleveland, OH

10. 10Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX

11. 11Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Brookline, MA

12. 12Division of Nephrology, Department of Medicine, University of Arizona, Tucson, AZ

13. 13Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD.

Funder

National Heart, Lung, and Blood Institute

National Institute of Neurological Disorders and Stroke

National Institute on Aging

JDRF Center for Excellence

National Institute of Diabetes and Digestive and Kidney Diseases

China International Medical Foundation-Renal Anemia Fund

China Scholarship Council

National Natural Science Foundation of China

University of Michigan

University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research

National Institutes of Health