Research Paper Volume 12, Issue 1 pp 106—121
Endothelial progenitor cells promote viability and nerve regenerative ability of mesenchymal stem cells through PDGF-BB/PDGFR-β signaling
- 1 Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
- 2 Central Laboratory, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
- 3 Department of Urinary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
Received: May 7, 2019 Accepted: December 5, 2019 Published: January 3, 2020https://doi.org/10.18632/aging.102604
How to Cite
Denervation-induced erectile dysfunction (ED) is a prevailing health problem. Our previous study revealed that endothelial progenitor cells (EPCs) promoted the effect of mesenchymal stem cells (MSCs) on restoration of denervation-induced ED in rats. However, underling mechanisms are still largely elusive. In this study, EPCs and MSCs were co-cultured and resorted to co-EPCs and co-MSCs. EPCs-derived paracrine factors containing PDGF-BB (platelet-derived growth factor) were detected, and MSCs were pre-treated with PDGF-BB, while co-MSCs were pre-treated with PDGFR inhibitor AG1296. Either viability or nerve regenerative ability of MSCs was evaluated. In addition, inhibition of either PI3K/Akt or MEK/Erk pathway was performed to evaluate the role of PI3K/Akt and MEK/Erk pathway in PDGF-BB-induced viability of MSCs. The results revealed that PDGF-BB significantly increased the proportion of PDGFR-β+ MSCs, and promoted both in-vitro and in-vivo viability, as well as nerve regenerative capacity and erectile function restoration of MSCs in rats. Inhibition of PI3K/Akt, MEK/Erk pathway or mTOR led to decrease of PDGF-BB/PDGFR-β induced viability of MSCs. To our knowledge, our study first demonstrates that EPCs promote viability and potential nerve regenerative ability of MSCs through PDGF-BB/PDGFR-β signaling and its downstream PI3K/Akt and MEK/Erk pathways. mTOR acts as a co-mediator in PI3K/Akt and MEK/Erk pathways.
bFGF: basic fibroblast growth factor; bFGFR: basic fibroblast growth factor receptor; CEBPα: CCAAT-enhancer binding protein alpha; CN: cavernous nerve; CNI: cavernous nerve injury; ED: erectile dysfunction; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPCs: endothelial progenitor cells; FABP4: fatty acid binding protein 4; HB-EGF: heparin binding epidermal growth factor; ICP: intracavernous pressure; PDGF: platelet-derived growth factor; PDGFR: platelet-derived growth factor receptor; RUNX2: runt-related transcription factor 2; PPARγ: peroxisome proliferator activated receptor; MAP: mean arterial pressure; MAP2: microtubule associated protein 2; mICP: maximal intracavernous pressure; MPG: major pelvic ganglia; MSCs: mesenchymal stem cells; tICP: total intracavernous pressure; TUBB3: tubulin beta 3.