Biology subjects

Zhang, M.-Z.

Publications and source records attributed to Zhang, M.-Z..

3 recordsLinked to original sources

bioRxiv2026

Targeting Protease-activated Receptor 4 (PAR4) Protects Against Acute Kidney Injury (AKI) in Ischemia Reperfusion Injury

Acute kidney injury (AKI) is a serious and common clinical syndrome that currently has no effective treatment. Emerging evidence links coagulation pathways to kidney injury, particularly through coagulation proteases. Protease-activated receptors (PARs) are a family of G-protein coupled receptors (GPCRs) that are activated by proteolytic cleavage of their N termini, exposing a tethered ligand that initiates receptor signaling. PARs have been shown to play a major role in inflammation, vascular regulation, and tissue injury. PARs play key roles in inflammation, vascular regulation, and tissue injury. Previous work from the Hamm laboratory demonstrated that PAR4 contributes to AKI progression, as PAR4 knockout mice were protected in both unilateral ureteral obstruction and ischemia-reperfusion-based models of kidney disease. In this study, we investigated the potential of a PAR4 antagonist, VU6073819, at mitigating AKI progression in an ischemia-reperfusion injury (IRI) mouse model. PAR4 antagonism not only alleviated kidney injury and inflammatory response, but it significantly improved the survival. These findings identify PAR4 as a promising therapeutic target for AKI.

pharmacology and toxicology↗

bioRxiv2022

Kidney collecting duct cells make vasopressin in response to NaCl induced hypertonicity

Vasopressin has traditionally been thought to be produced by the neurohypophyseal system and then released into the circulation where it regulates water homeostasis. The syndrome of inappropriate secretion of anti-diuretic hormone (vasopressin) raised the question if vasopressin could be produced outside of the brain and whether the kidney could be a source of vasopressin. We found that mouse and human kidneys expressed vasopressin mRNA. Using an antibody that detects the pre-pro-vasopressin, we found that immunoreactive pre-pro-vasopressin protein is found in mouse and human kidneys. Moreover, we found that murine collecting duct cells make biologically active vasopressin which increases in response to NaCl mediated hypertonicity, and that water restriction increases the abundance of kidney-derived vasopressin mRNA and protein expression in mouse kidneys. Thus, we provide evidence of biologically active production of kidney-derived vasopressin in kidney tubular epithelial cells.

physiology↗

bioRxiv2018

Human sperm chromatin forms spatially restricted nucleosome domains consistent with programmed nucleosome positioning

In human sperm, a fraction of its chromatin retains nucleosomes that are positioned on specific sequences containing genes and regulatory units essential for embryonic development. This nucleosome positioning (NP) feature provides an inherited epigenetic mark for sperm. However, it is not known whether there is a structural constraint for these nucleosomes and, if so, how they are localized in a three-dimensional (3D) context of the sperm nucleus. In this study, we examine the 3D organization of sperm chromatin and specifically determine its 3D localization of nucleosomes using structured illumination microscopy. A fraction of the sperm chromatin form nucleosome domains (NDs), visible as microscopic puncta ranging from 40 m to 700 m in diameter, and these NDs are precisely localized in the postacrosome region (PAR), outside the sperms core chromatin. Importantly, these types of NDs exist only in sperm from fertile men but not in sperm from sterile men. This study uncovers a new spatially restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm. This represents a novel form of epigenetic mark for healthy sperms and can provide a potential new therapeutic and diagnostic target for treating male infertility.

cell biology↗