| First Author | Schiessl IM | Year | 2018 |
| Journal | J Am Soc Nephrol | Volume | 29 |
| Issue | 5 | Pages | 1383-1396 |
| PubMed ID | 29444905 | Mgi Jnum | J:293544 |
| Mgi Id | MGI:6436991 | Doi | 10.1681/ASN.2017101069 |
| Citation | Schiessl IM, et al. (2018) Renal Interstitial Platelet-Derived Growth Factor Receptor-beta Cells Support Proximal Tubular Regeneration. J Am Soc Nephrol 29(5):1383-1396 |
| abstractText | BACKGROUND: The kidney is considered to be a structurally stable organ with limited baseline cellular turnover. Nevertheless, single cells must be constantly replaced to conserve the functional integrity of the organ. PDGF chain B (PDGF-BB) signaling through fibroblast PDGF receptor-beta (PDGFRbeta) contributes to interstitial-epithelial cell communication and facilitates regenerative functions in several organs. However, the potential role of interstitial cells in renal tubular regeneration has not been examined. METHODS: In mice with fluorescent protein expression in renal tubular cells and PDGFRbeta-positive interstitial cells, we ablated single tubular cells by high laser exposure. We then used serial intravital multiphoton microscopy with subsequent three-dimensional reconstruction and ex vivo histology to evaluate the cellular and molecular processes involved in tubular regeneration. RESULTS: Single-tubular cell ablation caused the migration and division of dedifferentiated tubular epithelial cells that preceded tubular regeneration. Moreover, tubular cell ablation caused immediate calcium responses in adjacent PDGFRbeta-positive interstitial cells and the rapid migration thereof toward the injury. These PDGFRbeta-positive cells enclosed the injured epithelium before the onset of tubular cell dedifferentiation, and the later withdrawal of these PDGFRbeta-positive cells correlated with signs of tubular cell redifferentiation. Intraperitoneal administration of trapidil to block PDGFRbeta impeded PDGFRbeta-positive cell migration to the tubular injury site and compromised the recovery of tubular function. CONCLUSIONS: Ablated tubular cells are exclusively replaced by resident tubular cell proliferation in a process dependent on PDGFRbeta-mediated communication between the renal interstitium and the tubular system. |
