Activation of STAT3 signaling pathway in the kidney of COVID-19 patients.

Autor: Salem F; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Li XZ; Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China., Hindi J; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Casablanca NM; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Zhong F; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., El Jamal SM; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Haroon Al Rasheed MR; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Li L; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, PA, USA., Lee K; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Chan L; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. lili.chan@mountsinai.org.; Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. lili.chan@mountsinai.org., He JC; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Cijiang.he@mssm.edu.; Renal Program, James J Peters VAMC, Bronx, NY, USA. Cijiang.he@mssm.edu.
Jazyk: angličtina
Zdroj: Journal of nephrology [J Nephrol] 2022 Apr; Vol. 35 (3), pp. 735-743. Date of Electronic Publication: 2021 Oct 09.
DOI: 10.1007/s40620-021-01173-0
Abstrakt: Background: Acute kidney injury is common in patients with COVID-19, however mechanisms of kidney injury remain unclear. Since cytokine storm is likely a cause of AKI and glomerular disease, we investigated the two major transcription factors, STAT3 and NF-kB, which are known to be activated by cytokines.
Methods: This is an observational study of the postmortem kidneys of 50 patients who died with COVID-19 in the Mount Sinai Hospital during the first pandemic surge. All samples were reviewed under light microscopy, electron microscopy, and immunofluorescence by trained renal pathologists. In situ hybridization evaluation for SARS-CoV-2 and immunostaining of transcription factors STAT3 and NF-kB were performed.
Results: Consistent with previous findings, acute tubular injury was the major pathological finding, together with global or focal glomerulosclerosis. We were not able to detect SARS-CoV-2 in kidney cells. ACE2 expression was reduced in the tubular cells of patients who died with COVID-19 and did not co-localize with TMPRSS2. SARS-CoV-2 was identified occasionally in the mononuclear cells in the peritubular capillary and interstitium. STAT3 phosphorylation at Tyr705 was increased in 2 cases in the glomeruli and in 3 cases in the tubulointerstitial compartments. Interestingly, STAT3 phosphorylation at Ser727 increased in 9 cases but only in the tubulointerstitial compartment. A significant increase in NF-kB phosphorylation at Ser276 was also found in the tubulointerstitium of the two patients with increased p-STAT3 (Tyr705).
Conclusions: Our findings suggest that, instead of tyrosine phosphorylation, serine phosphorylation of STAT3 is commonly activated in the kidney of patients with COVID-19.
(© 2021. Italian Society of Nephrology.)
Databáze: MEDLINE
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