miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy
Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2019/4946181 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850228461640089600 |
|---|---|
| author | Yingchun Zhu Jiang Xu Wenxing Liang Ji Li Linhong Feng PengXi Zheng Tingting Ji Shoujun Bai |
| author_facet | Yingchun Zhu Jiang Xu Wenxing Liang Ji Li Linhong Feng PengXi Zheng Tingting Ji Shoujun Bai |
| author_sort | Yingchun Zhu |
| collection | DOAJ |
| description | Recently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN. |
| format | Article |
| id | doaj-art-2bbb7bee0bd3427a974f35393975c7db |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-2bbb7bee0bd3427a974f35393975c7db2025-08-20T02:04:31ZengWileyInternational Journal of Endocrinology1687-83371687-83452019-01-01201910.1155/2019/49461814946181miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic NephropathyYingchun Zhu0Jiang Xu1Wenxing Liang2Ji Li3Linhong Feng4PengXi Zheng5Tingting Ji6Shoujun Bai7Department of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Rehabilitation, Huai’an Second People’s Hospital, The Affiliated Hospital of Xuzhou Medical University, Huai’an, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaDepartment of Nephrology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, 1158 Gongyuan East Road, Qingpu District, Shanghai 201700, ChinaRecently, microRNAs have been recognized as crucial regulators of diabetic nephropathy (DN) development. Epithelial-to-mesenchymal transition (EMT) can play a significant role in tubulointerstitial fibrosis, and it is a hallmark of diabetic nephropathy progression. Nevertheless, the function of miR-98-5p in the modulation of EMT and renal fibrosis during DN remains barely investigated. Hence, identifying the mechanisms of miR-98-5p in regulating EMT and fibrosis is of huge significance. In our present research, decreased miR-98-5p was demonstrated in db/db mice and mice mesangial cells treated with the high dose of glucose. Meanwhile, activated EMT and increased fibrosis was accompanied with the decrease of miR-98-5p in vitro and in vivo. Additionally, to further find out the roles of miR-98-5p in DN development, overexpression of miR-98-5p was applied. Firstly, in vivo investigation exhibited that elevation of miR-98-5p restrained proteinuria, serum creatinine, BUN, the EMT process, and fibrosis. Furthermore, high glucose was able to promote mice mesangial cell proliferation, EMT process, and induced renal fibrosis, which could be prevented by overexpression of miR-98-5p. Moreover, high mobility group A (HMGA2) can exhibit an important role in diverse biological processes. Here, HMGA2 was investigated as a target of miR-98-5p currently. Luciferase reporter assay was conducted and the correlation of miR-98-5p and HMGA2 was validated. Moreover, it was displayed that HMGA2 was remarkably elevated in db/db mice and mice mesangial cells. Furthermore, miR-98-5p strongly depressed HMGA2 protein and mRNA levels in mice mesangial cells. Overall, these revealed miR-98-5p could suppress the EMT process and renal fibrosis through targeting HMGA2 in DN.http://dx.doi.org/10.1155/2019/4946181 |
| spellingShingle | Yingchun Zhu Jiang Xu Wenxing Liang Ji Li Linhong Feng PengXi Zheng Tingting Ji Shoujun Bai miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy International Journal of Endocrinology |
| title | miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy |
| title_full | miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy |
| title_fullStr | miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy |
| title_full_unstemmed | miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy |
| title_short | miR-98-5p Alleviated Epithelial-to-Mesenchymal Transition and Renal Fibrosis via Targeting Hmga2 in Diabetic Nephropathy |
| title_sort | mir 98 5p alleviated epithelial to mesenchymal transition and renal fibrosis via targeting hmga2 in diabetic nephropathy |
| url | http://dx.doi.org/10.1155/2019/4946181 |
| work_keys_str_mv | AT yingchunzhu mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT jiangxu mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT wenxingliang mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT jili mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT linhongfeng mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT pengxizheng mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT tingtingji mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy AT shoujunbai mir985palleviatedepithelialtomesenchymaltransitionandrenalfibrosisviatargetinghmga2indiabeticnephropathy |