{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tang C"],"funding":["Central Finance supports Local Colleges, and Universities Talent Development Funding from Heilongjiang Provincial Department of Finance","Doctoral Research Foundation of Mudanjiang Medical University","Graduate Innovation Funding of Mudanjiang Medical University","National Natural Science Foundation of China","Central Finance","The Torch Program of Mudanjiang Medical College Science Foundation","Torch Program of Mudanjiang Medical College Science Foundation","Basic Scientific Research Project of the University, which belongs to Heilongjiang","The Basic Scientific Research Project of University belongs to Heilongjiang","The Doctoral Research Foundation of Mudanjiang Medical University"],"pagination":["3270"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9775671"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(12)"],"pubmed_abstract":["Excessive accumulation of the extracellular matrix (ECM) is a crucial pathological process in chronic kidney diseases, such as diabetic nephropathy, etc. The underlying mechanisms of how to decrease ECM deposition to improve diabetic nephropathy remain elusive. The present study investigated whether cyclopentanone compound H8 alleviated ECM over-deposition and fibrosis to prevent and treat diabetic nephropathy. HK-2 cell viability after treatment with H8 was measured by an MTT assay. ECM alterations and renal fibrosis were identified in vitro and in vivo. A pharmacological antagonist was used to detect associations between H8 and the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. H8 binding was identified through computer simulation methods. Studies conducted on high glucose and transforming growth factor β1 (TGF-β1)-stimulated HK-2 cells revealed that the p38MAPK inhibitor SB 202190 and H8 had similar pharmacological effects. In addition, excessive ECM accumulation and fibrosis in diabetic nephropathy were remarkably improved after H8 administration in vivo and in vitro. Finally, the two molecular docking models further proved that H8 is a specific p38MAPK inhibitor that forms a hydrogen bond with the LYS-53 residue of p38MAPK. The cyclopentanone compound H8 alleviated the over-deposition of ECM and the development of fibrosis in diabetic nephropathy by suppressing the TGF-β/p38MAPK axis."],"journal":["Biomedicines"],"pubmed_title":["A Cyclopentanone Compound Attenuates the Over-Accumulation of Extracellular Matrix and Fibrosis in Diabetic Nephropathy via Downregulating the TGF-β/p38MAPK Axis."],"pmcid":["PMC9775671"],"funding_grant_id":["2018-KYYWF-0136","2020GSP09","2020YJSCX-MY07","2022-MYHJ-006","81770828","2021-MYBSKY-060"],"pubmed_authors":["Wang M","Liu H","Liu J","Tang C","Chu Y","Wu D","Zhang C","Yuan X","Li L","Wu Y"],"additional_accession":[]},"is_claimable":false,"name":"A Cyclopentanone Compound Attenuates the Over-Accumulation of Extracellular Matrix and Fibrosis in Diabetic Nephropathy via Downregulating the TGF-β/p38MAPK Axis.","description":"Excessive accumulation of the extracellular matrix (ECM) is a crucial pathological process in chronic kidney diseases, such as diabetic nephropathy, etc. The underlying mechanisms of how to decrease ECM deposition to improve diabetic nephropathy remain elusive. The present study investigated whether cyclopentanone compound H8 alleviated ECM over-deposition and fibrosis to prevent and treat diabetic nephropathy. HK-2 cell viability after treatment with H8 was measured by an MTT assay. ECM alterations and renal fibrosis were identified in vitro and in vivo. A pharmacological antagonist was used to detect associations between H8 and the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. H8 binding was identified through computer simulation methods. Studies conducted on high glucose and transforming growth factor β1 (TGF-β1)-stimulated HK-2 cells revealed that the p38MAPK inhibitor SB 202190 and H8 had similar pharmacological effects. In addition, excessive ECM accumulation and fibrosis in diabetic nephropathy were remarkably improved after H8 administration in vivo and in vitro. Finally, the two molecular docking models further proved that H8 is a specific p38MAPK inhibitor that forms a hydrogen bond with the LYS-53 residue of p38MAPK. The cyclopentanone compound H8 alleviated the over-deposition of ECM and the development of fibrosis in diabetic nephropathy by suppressing the TGF-β/p38MAPK axis.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2024-11-08T20:13:32.642Z","creation":"2024-11-08T20:13:32.642Z"},"accession":"S-EPMC9775671","cross_references":{"pubmed":["36552026"],"doi":["10.3390/biomedicines10123270"]}}