Inhibition of miRNA-21 prevents fibrogenic activation in podocytes and tubular cells in IgA nephropathy.
Podocytopathy and tubular interstitial fibrosis impact on renal outcomes of IgA nephropathy (IgAN). We found that level of miR-21 was up regulated in both glomerular and tubular-interstitial tissues of patients with IgAN. Enhanced expression of miR-21 mainly located in podocytes and tubular cells. Mesangial cell derived cytokines contributed to the increase of miR-21 in podocytes and HK2 cells. IgA-HMC medium prepared with pIgA from IgAN, lead to obvious fibrogenic activation, evidenced by the loss of Podocin and CD2AP in podocytes, loss of E-cadherin and Megalin in HK2 cells and increase of FN and Col I in both cells. miR-21 targeted PTEN in these cells. Expression of PTEN was decreased and phosphorylation of Akt was increased in podocytes and HK2 cells exposed to the medium prepared with pIgA from IgAN. Inhibition of miR-21 preserved the expression of PTEN, prevented the activation of Akt and inhibited the fibrogenic activation in podocytes and HK2 cells exposed to the IgA-HMC medium prepared with pIgA from IgAN. In conclusion, our study suggests that inhibition of miR-21 prevents fibrogenic activation in podocytes and tubular cells by preventing PTEN/Akt pathway activation in IgAN.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Hao
H
Bao
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Shuai
S
Hu
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Changming
C
Zhang
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Shaolin
S
Shi
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Weisong
W
Qin
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Caihong
C
Zeng
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Ke
K
Zen
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. Electronic address: Zhihong-liu@hotmail.com.
Zhihong
Z
Liu
D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000276:immunology / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000276:immunology; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000276:immunology; D050199:Podocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction; D015854:Up-Regulation
D016207:Cytokines; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Fibrogenic activation; IgA nephropathy; miRNA-21