Platelet-derived growth factor-C contributes to kidney inflammation in experimental hypertension with little effect on the peritubular capillary network.

BACKGROUND AND AIMS: Platelet-Derived Growth Factor (PDGF)-C plays a significant role in kidney fibrosis, angiogenesis, and hypertension. While its involvement in the healing of damaged glomerular capillaries is well recognized, its function in kidney peritubular capillaries (PTCs) remains less understood. Therefore, this study investigates the role of PDGF-C in PTCs under both homeostatic conditions and experimentally angiotensin II (AngII)-induced hypertension.

MATERIALS AND

METHODS

We utilized mice with systemic PDGF-C antagonism or conditional deletion of endothelial-derived PDGF-C (Cdh5-cre::Pdgfcflox/flox) in an AngII-induced hypertension model. The PTC network, glycocalyx, and inflammatory parameters in the kidneys were analyzed and quantified using qPCR, electron microscopy, and fluorescence microscopy.

RESULTS

Systemic antagonism of PDGF-C in the AngII model reduced peritubular accumulation of PDGF receptor-expressing mesenchymal cells and the expression of Ccl2, Plat and Nos3, while PTC density and glycocalyx-regulating genes remained unaffected. Conditional deletion of endothelial cell-derived PDGF-C did not affect peritubular accumulation of mesenchymal cells, blood pressure or genes associated with angiogenesis; it also had no impact on the PTC network or glycocalyx. Notably, a reduction in inflammatory infiltrates was observed in the hypertensive Cdh5-cre::Pdgfcflox/flox -mice.

CONCLUSION

Despite influencing certain parameters critical for endothelial homeostasis, such as PDGFR+ pericyte recruitment following systemic PDGF-C antagonism during hypertension, PDGF-C has minimal effects on the PTC network. Conversely, both systemic and endothelial cell-derived PDGF-C modulate the inflammatory response associated with hypertension in the kidney. Our findings help mitigate safety concerns about pharmacological PDGF-C targeting and its impact on peritubular capillaries.