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ResearchIn-Press PreviewNephrology Open Access | 10.1172/JCI165836
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Gui, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Fu, H. in: JCI | PubMed | Google Scholar |
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Palanza, Z. in: JCI | PubMed | Google Scholar |
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Tao, J. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Lin, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Min, W. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Qiao, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Bonin, C. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Hargis, G. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Wang, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Yang, P. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Kreutzer, D. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Wang, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Liu, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Yu, Y. in: JCI | PubMed | Google Scholar
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Liu, Y. in: JCI | PubMed | Google Scholar |
1Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, United States of America
2Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America
3Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, United States of America
4Early Translation Branch, National Center for Advancing Translational Sciences, Rockville, United States of America
5State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Dru, China Pharmaceutical University, Nanjing, China
6Department of Surgery, University of Connecticut School of Medicine, Farmington, United States of America
7University of Connecticut School of Medicine, Farmington, United States of America
8Division of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Pittsburgh, United States of America
9State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Dr, China Pharmaceutical University, Nanjing, China
10Department of Pharmacology, School of Medicine, Yale University, New Haven, United States of America
11Department of Chemistry & Biochemistry, University of Delaware, Newark, United States of America
Find articles by Zhou, D. in: JCI | PubMed | Google Scholar |
Published May 7, 2024 - More info
The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cells activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could impact nidogen-1 accessibility. Phosphoproteomics revealed that the ‘AKI protector’ Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin β1 to induce Wnts in tubules to mitigate AKI. Altogether, our results support that fibroblast-selective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis.