Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosomes released by injured epithelial cells promote proliferation, a-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-b1 mRNA among other yet to be identified moieties. This study suggests that TGF-b1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis.

Am J Transplant. 2020;00:1-4. | 1 amjtransplant.com | BACKG ROU N DCoronavirus Disease 2019 (COVID-19) is a novel viral disease with over 93 000 confirmed cases worldwide,1 in which knowledge regarding disease epidemiology and clinical presentation has been evolving in the past 4 months since the initial identification. In the general population, the reported case fatality rate is about 1%-6%.2 Solid organ transplant (SOT) recipients are under chronic immunosuppression, and respiratory infections may present atypically, often with two or more infectious processes presenting simultaneously.3 There have been currently only a couple of reports of COVID-19 among SOT recipients. Hence, in such a high risk population, a strong clinical suspicion is crucial. Herein we present the case of a COVID-19 infection in a kidney transplant recipient. | C A S E REP ORTA 50-year-old man with end-stage renal disease due to IgA nephropathy, recipient of a 3rd deceased-donor kidney transplant in 2016 with serum creatinine (Cr) of 1.3 mg/dL and estimated glomerular filtration rate (eGFR) of 60 mL/min, was admitted on February 28 to the emergency room (ER) with a 24-hour history of fever (38.2°C/100.8°F) and vomiting. He reported no other symptoms, nor had a history of travels abroad nor exposure to patients infected or suspected of contagious COVID-19. Previous medical history included an elective splenectomy performed in 2003 due to immune thrombocytopenia, and an Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) in 2005, treated with rituximab and withdrawal of immunosuppression, achieving complete response of the PTLD, but leading to rejection and failure of the 2nd kidney graft. Following PTLD remission and a negative EBV viral load, he received a 3rd kidney transplant with induction immunosuppression (IS) with thymoglobulin, tacrolimus, everolimus and steroids, and maintenance IS with tacrolimus, everolimus and prednisone 5 mg QD. He was also under treatment with losartan 50 mg bid due to arterial hypertension.At first evaluation in the ER the patient presented signs of mild dehydration. Physical examination was otherwise unremarkable, including breath sounds on chest auscultation. On blood workup acute phase reactants were normal, such as a C-reactive protein (CRP) of <0.50 mg/dL (normal range <1.0 mg/dL) and white blood cells (WBC) count of 8.58 × 10 9 /L, but a mild kidney function impairment (Cr

Remarkably, the mortality in our cohort was lower than that previously reported 4 and similar to the general population, 5 even though some patients are still admitted. Larger studies are underway to provide robust information on the prognosis and management of kidney transplant recipients with COVID-19.