Biology subjects

Wehler, P.

Publications and source records attributed to Wehler, P..

3 recordsLinked to original sources

bioRxiv2025

A complex osteoporotic milieu is associated with arterial stiffening and PDGF-BB-mediated calcification of human smooth muscle cells

Accumulating evidence links skeletal and vascular aging, yet the pathological cross-talk between osteoporotic bone and vascular calcification remains insufficiently understood. In this retrospective exploratory study, we show that osteoporotic individuals exhibit a distinct systemic milieu characterized by elevated eosinophil, neutrophil, and platelet counts, as well as altered levels of sCD40L, PDGF-BB, osteopontin, and SDF-1. These changes correlate with both bone metabolism and arterial stiffness, indicating a multifactorial bone-vascular interplay. Moreover, osteoporotic sera accelerated calcification of human vascular smooth muscle cells in vitro, with PDGF-BB emerging as a central mediator. Inhibition of PDGF-BB downstream signaling blocked this effect, suggesting a mechanistic role of PDGF-BB in linking the osteoporotic milieu to vascular calcification. Conceptualizing this cross-talk as a complex adaptive system advances our understanding of the disease dynamics between localized bone loss and vascular pathologies. Furthermore, it may guide therapeutic strategies, with PDGF-BB as a potential target, to support healthier aging.

cell biology↗

bioRxiv2021

Red-shifted iLOV mutants have decreased brightness disrupting their use in live cell imaging

iLOV is a flavin mononucleotide-binding fluorescent protein used for in vivo cellular imaging similar to the green fluorescent protein. To expand the range of applications of iLOV, spectrally tuned red-shifted variants are desirable to have reduced phototoxicity and better tissue penetration. In this report, we experimentally tested two iLOV mutants, iLOVL470T/Q489K and iLOVV392K/F410V/A426S, which were previously computationally proposed by Khrenova et al. (DOI: 10.1021/acs.jpcb.7b07533) to have red-shifted excitation and emission spectra. We found that mutants bearing the V392K mutation lost the ability to bind FMN. While iLOVL470T/Q489K is about 20% brighter compared to WT iLOV in vitro, it exhibits a blue shift in contrast to QM/MM predictions. Additionally, both mutants are expressed at low levels and have undetectable fluorescence in living cells, which prevents their utilization in imaging applications. Our results suggest that rational fluorescent protein design efforts can benefit from in silico protein stability and ligand affinity calculations.

biophysics↗

bioRxiv2019

BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients

Reactivation of the BK polyomavirus is known to lead to severe complications in kidney transplant patients. The current treatment strategy relies on decreasing the immunosuppression to allow the immune system to clear the virus. Recently, we demonstrated a clear association between the resolution of BKV reactivation and reconstitution of BKV-specific CD4+ T-cells. However, which factors determine the duration of viral infection clearance remains so far unclear. Here we apply a combination of in-depth multi-parametric flow cytometry and NGS-based CDR3 beta chain receptor repertoire analysis of BKV-specific T-cells to a cohort of 7 kidney transplant patients during the clinical course of BKV reactivation. This way we followed TCR repertoires at single clone levels and functional activity of BKV-specific T-cells during the resolution of BKV infection. The duration of BKV clearance did not depend on the number of peripheral blood BKV-specific T-cells nor on a few immunodominant BKV-specific T-cell clones. Rather, the T-cell receptor repertoire diversity and exhaustion status of BKV-specific T-cells affected the duration of viral clearance: high clonotype diversity and lack of PD1 and TIM3 exhaustion markers on BKV-specific T-cells was associated with short clearance time. Our data thus demonstrate how the diversity and the exhaustion state of the T-cells can determine the clinical course of BKV infection.

immunology↗