Repression of miR-764-5p by enhancing IGF1R and cochaperone CHIP expression in mesenchymal stem cells (MSCs) regulates cardioprotective effects in Aging-Spontaneously Hypertensive rats model
Abstract Age-associated cardiovascular disease (CVD) progression is marked by increased misfolded proteins and reduced growth factor receptor activity. Evidence links the co-chaperone CHIP and insulin-like growth factor-1 receptor (IGF1R) to stem cell dynamics and function through miR-764-5p in rat adipose-derived stem cells (rADSCs) remains largely unknown. We observed that short-term hypoxia (6 h) downregulated miR-764-5p in rADSCs, while normoxia conditions led to miR-764-5p upregulation, targeting the 3' UTR region of IGF1R and STUB1/CHIP. qRT-PCR confirmed altered mRNA expression. Overexpression of anti-miR-764-5p enhanced rADSC survival via CHIP and IGF1R upregulation, while miR-764-5p mimic increased ROS generation and apoptosis. HIF1α transcription factor downregulated miR-764-5p under short-term hypoxia. Administering rADSCsanti−miR−764−5p in aging-spontaneously hypertensive rats (SHR) via tail-vein injection demonstrated cardioprotective effects, reducing cardiac hypertrophy, fibrosis, and apoptosis and it could be the potential to act as a regenerative medicine. In conclusion, suppressing miR-764-5p enhances IGF1R expression and CHIP activity in rADSCs, mitigating cardiac hypertrophy and remodeling in the aging-SHR model..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 12. Feb. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Chih-Yang [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.21203/rs.3.rs-3605059/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA041703650 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA041703650 | ||
| 003 | DE-627 | ||
| 005 | 20240212130415.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231130s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-3605059/v1 |2 doi | |
| 035 | |a (DE-627)XRA041703650 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-3605059/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Chih-Yang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Repression of miR-764-5p by enhancing IGF1R and cochaperone CHIP expression in mesenchymal stem cells (MSCs) regulates cardioprotective effects in Aging-Spontaneously Hypertensive rats model |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Age-associated cardiovascular disease (CVD) progression is marked by increased misfolded proteins and reduced growth factor receptor activity. Evidence links the co-chaperone CHIP and insulin-like growth factor-1 receptor (IGF1R) to stem cell dynamics and function through miR-764-5p in rat adipose-derived stem cells (rADSCs) remains largely unknown. We observed that short-term hypoxia (6 h) downregulated miR-764-5p in rADSCs, while normoxia conditions led to miR-764-5p upregulation, targeting the 3' UTR region of IGF1R and STUB1/CHIP. qRT-PCR confirmed altered mRNA expression. Overexpression of anti-miR-764-5p enhanced rADSC survival via CHIP and IGF1R upregulation, while miR-764-5p mimic increased ROS generation and apoptosis. HIF1α transcription factor downregulated miR-764-5p under short-term hypoxia. Administering rADSCsanti−miR−764−5p in aging-spontaneously hypertensive rats (SHR) via tail-vein injection demonstrated cardioprotective effects, reducing cardiac hypertrophy, fibrosis, and apoptosis and it could be the potential to act as a regenerative medicine. In conclusion, suppressing miR-764-5p enhances IGF1R expression and CHIP activity in rADSCs, mitigating cardiac hypertrophy and remodeling in the aging-SHR model. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Barik, Parthasarathi |4 aut | |
| 700 | 1 | |a Kuo, Wei-Wen |4 aut | |
| 700 | 1 | |a Kuo, Chia-Hua |4 aut | |
| 700 | 1 | |a Hsieh, Dennis |4 aut | |
| 700 | 1 | |a Day, Cecilia |4 aut | |
| 700 | 1 | |a Daddam, Jayasimharayalu |4 aut | |
| 700 | 1 | |a Chen, Michael |4 aut | |
| 700 | 1 | |a Padma, V. Vijaya |4 aut | |
| 700 | 1 | |a Shibu, Marthandam |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2024) vom: 12. Feb. |
| 773 | 1 | 8 | |g year:2024 |g day:12 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-3605059/v1 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 12 |c 02 | ||