Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis.

Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen (O2) delivery and combat tissue hypoxia. Here, we report that erythrocyte transglutminase-2 (eTG2)-mediated PTM is essential to trigger O2 delivery by promoting bisphosphoglycerate mutase proteostasis and the Rapoport-Luebering glycolytic shunt for adaptation to hypoxia, in healthy humans ascending to high altitude and in two distinct murine models of hypoxia. In a pathological hypoxia model with chronic kidney disease (CKD), eTG2 is critical to combat renal hypoxia-induced reduction of Slc22a5 transcription and OCNT2 protein levels via HIF-1α-PPARα signaling to maintain carnitine homeostasis. Carnitine supplementation is an effective and safe therapeutic approach to counteract hypertension and progression of CKD by enhancing erythrocyte O2 delivery. Altogether, we reveal eTG2 as an erythrocyte protein stabilizer orchestrating O2 delivery and tissue adaptive metabolic reprogramming and identify carnitine-based therapy to mitigate hypoxia and CKD progression.

Platelet-rich plasma: clinical applications in dentistry.

BACKGROUND: Platelet-rich plasma, or PRP, has become a valuable adjunct in wound healing in dentistry. Postsurgically, blood clots initiate the healing and regeneration of hard and soft tissues. Clinicians and scientists are investigating the use of PRP in dentistry as a way to enhance the body's natural wound-healing mechanisms. TYPES OF ARTICLES REVIEWED: The authors reviewed scientific articles that discuss the basic knowledge of wound healing mechanisms and that directly studied the growth factors shown to be concentrated in PRP. They also reviewed articles written by clinicians and researchers in dentistry fields, including oral and maxillofacial surgery and periodontics to determine applications of PRP in the field of dentistry. RESULTS: All of the reviewed articles expressed promise in PRP use and in the growth factors expressed by the platelets concentrated in PRP-namely platelet-derived growth factor, or PDGF, and transforming growth factor-beta, or TGF-beta--as an adjunct to postsurgical wound healing. Both PDGF and TGF-beta have been shown in vivo to accelerate wound healing through different mechanisms. The development of an autologous PRP has been shown to be relatively easy, to be effective as a surgical adjunct, to retain high levels of the desired growth factors after preparation and to be clinically effective in accelerating postsurgical healing in both periodontal and oral surgery applications. CLINICAL IMPLICATIONS: PRP has proven to be effective at improving surgical results in a variety of procedures in the field of oral and maxillofacial surgery. PRP also shows promise in periodontal regenerative therapy and should continue to be studied by scientists and clinicians alike.