Megalin is involved in angiotensinogen-induced, angiotensin II-mediated ERK1/2 signaling to activate Na+-H+ exchanger 3 in proximal tubules

aDepartment of Applied Molecular Medicine

bDepartment of Structural Pathology

cDepartment of Clinical Nutrition Science

dDepartment of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata

eThe Institute of Medical Science

fThe Institute of Medical Science and Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Correspondence to Akihiko Saito, MD, PhD, Department of Applied Molecular Medicine, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8510, Japan. Tel: +81 25 227 0914; fax: +81 25 227 0914; e-mail: [email protected]

Abbreviations: ACE, angiotensin-converting enzyme; AGT, angiotensinogen; Ang, angiotensin; AT1R, angiotensin II type 1 receptor; BP, blood pressure; BSA, bovine serum albumin; Ctl, control; ERK, extracellular signal-regulated kinase; LC, liquid chromatography; MegKO, megalin knockout; MS, tandem mass spectrometry; NEP, neprilysin; NHE3, Na+-H+ exchanger 3; PEP, prolyl endopeptidase; p-ERK, phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204); PRM, parallel reaction monitoring; PTEC, proximal tubular epithelial cell; RAS, renin–angiotensin system; rec-mAGT, recombinant mouse AGT; SD, standard deviation; SPR, surface plasmon resonance; t-ERK, p44/42 MAPK (Erk1/2)

Received 13 December, 2022

Revised 24 July, 2023

Accepted 17 August, 2023

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