Research Paper Volume 15, Issue 23 pp 14019—14038
Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats
- 1 Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
- 2 Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
- 3 Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
- 4 School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
- 5 Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
- 6 Department of Nursing, Mei Ho University, Pingtung, Taiwan
- 7 Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- 8 Department of Cardiology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- 9 Department of Biotechnology, Bharathiar University, Coimbatore, India
- 10 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
- 11 Department of Biotechnology, Asia University, Taichung, Taiwan
- 12 Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
Received: September 1, 2021 Accepted: October 4, 2023 Published: December 11, 2023
https://doi.org/10.18632/aging.205287How to Cite
Copyright: © 2023 Barik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Aging-associated cardiovascular diseases depend on the longitudinal deterioration of stem cell dynamics. The entire mechanism behind it is not completely understood. However, many studies suggest that endocrine pathways, particularly the insulin-like growth factor-1(IGF1) signaling pathway are involved in cardioprotection, especially in stem-cell treatments. Here, we investigated the role of a co-chaperone, carboxyl-terminus of Hsp70 interacting protein (CHIP) in the aspects of growth factor secretion and receptor stabilization in mesenchymal stem cells (MSCs). Briefly, we overexpressed CHIP in rat adipose-derived stem cells (rADSCs) and explored the consequences in vitro, and in vivo, in spontaneously hypertensive rats (SHR). Our data revealed that CHIP overexpression in rADSCs promoted the secretion of insulin-like growth factor-1 (IGF1) and IGF binding protein-3 (IGFBP3) as per immunoblot/cytokine array analysis. We also found that these results were dependent on the nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in rADSCs. Further, the CHIP co-chaperone was also involved in the stabilization of the receptor of IGF1 (IGF1R); interactions between the beta transmembrane region of IGF1R, and the tetracopeptide repeat (TPR) domain of CHIP were evident. Importantly, after the transplantation of lentiviral CHIP overexpression of rADSCs (rADSCsCHIP-WT) into nine months aging-SHR led to an increase in their cardiac function - increased ejection fraction and fractional shortening (≈15% vs. control SHR) - as well as a decrease in their heart size and heart rate, respectively. Altogether, our results support the use of CHIP overexpressing stem cells for the mitigation of cardiac hypertrophy and remodeling associated with late-stage hypertension.