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pmid:34580604

PP2 Ameliorates Renal Fibrosis by Regulating the NF-κB/COX-2 and PPARγ/UCP2 Pathway in Diabetic Mice.

Jinying Wei · Xinna Deng · Yang Li · Runmei Li · Zhaohua Yang · Xiuyuan Li · Shan Song · Yonghong Shi · Huijun Duan · Haijiang Wu

Oxidative medicine and cellular longevity · 2021 doi:10.1155/2021/7394344

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
PP2 Ameliorates Renal Fibrosis by Regulating the NF-κB/COX-2 and PPARγ/UCP2 Pathway in Diabetic Mice.
doi
10.1155/2021/7394344
pmid
34580604
authors array · 10 items
[0]
Jinying Wei
[1]
Xinna Deng
[2]
Yang Li
[3]
Runmei Li
[4]
Zhaohua Yang
[5]
Xiuyuan Li
[6]
Shan Song
[7]
Yonghong Shi
[8]
Huijun Duan
[9]
Haijiang Wu
journal
Oxidative medicine and cellular longevity
year
2021
abstract
Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN). We aimed to evaluate the effects of PP2 on renal fibrosis of DN. GSE33744 and GSE86300 were downloaded from the GEO database. Firstly, 839 DEGs were identified between nondiabetic and diabetic mice renal glomerular samples. COX-2 was selected to assess the effects of PP2 on renal glomerulosclerosis. In db/db mice, PP2 decreased the expression of COX-2, phosphorylated p65, and fibrotic proteins, accompanied with attenuated renal glomerulosclerosis. In cultured glomerular mesangial cells, high glucose- (HG-) induced p65 phosphorylation and COX-2 expression were attenuated by PP2 or NF-κB inhibitor PDTC. PP2, PDTC, or COX-2 inhibitor NS-398 ameliorated abnormal proliferation and expression of fibrotic proteins induced by HG. Secondly, 238 DEGs were identified between nondiabetic and diabetic mice renal cortex samples. UCP2 was selected to assess the effects of PP2 on renal tubulointerstitial fibrosis. In db/db mice, PP2 decreased the expression of PPARγ and UCP2, accompanied with attenuated renal tubulointerstitial fibrosis and EMT. In cultured proximal tubular cells, HG-induced PPARγ and UCP2 expression was inhibited by PP2 or PPARγ antagonist GW9662. PP2, GW9662, or UCP2 shRNA ameliorated HG-induced EMT. These results indicated that PP2 ameliorated renal fibrosis in diabetic mice.
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Cross-species transcriptional networks in Diabetic Glomerulopathy in mouse and man
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Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications
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with attenuated renal glomerulosclerosis. In cultured glomerular mesangial cells, high glucose- (H
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PARγ antagonist GW9662. PP2, GW9662, or UCP2 shRNA ameliorated HG-induced EMT. These results in
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