Biology subjects

Ozkan, M.

Publications and source records attributed to Ozkan, M..

4 recordsLinked to original sources

bioRxiv2025

An extracellular matrix coating similar to articular cartilage inhibits the differentiation of myofibroblasts and limits the development of implant-induced fibrosis

Fibrosis is involved in 45% of deaths in the United States, with no treatment options to reverse progression of the disease. Implantable devices (such as joint replacements, chips, stents, artificial organs, biosensors, catheters, heart valves, scaffolds for tissue engineering, etc.) can trigger a foreign body response, in which fibrotic tissue covers the implant and impedes its function. Myofibroblast are a key cellular component of scar tissue. To explore the relationship between extracellular matrix-based coatings and fibrosis, we coated tissue-culture surfaces using a library of extracellular matrix (ECM) proteins and then performed an in-vitro screen for myofibroblast differentiation on the coated surfaces as an indicator of fibrotic potential. The protein and proteoglycan components of cartilage (collagen II, biglycan, decorin, and chondroitin sulfate) were individually anti-fibrotic. Further, mixtures of collagen II, biglycan, decorin, and chondroitin sulfate inhibited myofibroblast differentiation to a greater degree than collagen II, biglycan, decorin, or chondroitin sulfate as individual coatings. Next, we performed an in-vivo model of a foreign-body response. Implanting an uncoated implant subcutaneously into mice resulted in a thicker layer of fibrotic scar tissue than implants coated with a cartilage-like ECM mixture. Our results indicate that the ECM microenvironment is key to the initiation, progression, and maintenance of fibrosis.

immunology↗

bioRxiv2025

Primary and secondary auditory cortex connectivity with brain regions involved in cognitive and emotional processing: in mouse and human

Auditory cortex connectivity extends beyond the processing of acoustic stimuli, playing a crucial role in cognitive and emotional regulation through its interactions with higher-order brain regions. Although the neural mechanisms underlying acoustic information processing along the auditory pathway are well-documented, the connections supporting auditory-related cognitive and emotional processing, particularly in comparative studies between mice and human adults, are not yet fully clarified. In this study, we aim to investigate connections between the auditory cortex and brain regions involved in cognitive and emotional processing using retrograde fluoro-gold (FG) tracer in mice and 3-tesla high-resolution diffusion tensor tractography (DTI) in human adults. The FG injections into the primary (AI)/ secondary (AII) auditory cortices showed afferent connections with cortical (olfactory bulb, piriform, orbitofrontal, cingulate, motor, primary somatosensory, insular, visual, parietal, entorhinal and perirhinal cortices), subcortical (amygdala, hippocampus, globus pallidus, claustrum, bed nucleus of stria terminalis, diagonal band of the Broca and medial septal nucleus) and brainstem (raphe nuclei, pedunculopontine nucleus and locus coeruleus) structures. The DTI data obtained from human adults mostly corresponded with the experimental findings. Auditory cortical processing integrates auditory signals with other sensory, limbic and motor inputs. The connections collectively may suggest its role in cognitive and emotional functions. The auditory cortex is likely a critical hub within the neural circuitry underlying multisensory integration, decision-making, prediction, learning and memory functions. Understanding the connectivity of the auditory cortex can deepen our insight into its contribution to cognitive/emotional functions, offering new perspectives on the underlying mechanism linking hearing deficits with cognitive/emotional disorders.

neuroscience↗

bioRxiv2022

A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and foodways. We present thirteen ancient genomes (c.8500-7500 calBCE) from Pre-Pottery Neolithic Cayonu in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Cayonu was a genetically diverse population, carrying a mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organised along biological family lines. We document bodily interventions such as head-shaping and cauterization among the individuals examined, reflecting Cayonus cultural ingenuity. Finally, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesise that Upper Mesopotamias cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.

genetics↗

bioRxiv2021

Myofibroblast differentiation is governed by adhesion mechanics, and inhibition of the stress sensor Talin2 reverses lung fibrosis

Fibrosis is involved in 45% of deaths in the United States, and no treatment exists to reverse progression of the disease. In order to find novel targets for fibrosis therapeutics, we developed a model for the differentiation of monocytes to myofibroblasts that allowed us to screen for proteins involved in myofibroblast differentiation. Inhibition of a novel protein target generated by our model, talin2, reduces myofibroblast morphology, -smooth muscle actin content, collagen I content, and lowers the pro-fibrotic secretome of myofibroblasts. We find that knockdown of talin2 de-differentiates myofibroblasts, talin2 knockdown reverses bleomycin-induced lung fibrosis in mice, and Tln2 -/-mice are resistant to unilateral ureteral obstruction-induced kidney fibrosis and are resistant to bleomycin-induced lung fibrosis. Talin2 inhibition is a potential treatment for reversing lung and kidney fibroses. One Sentence SummarySilencing the stress sensor Talin2 reverses myofibroblast differentiation and existing fibrosis.

immunology↗