Extraneural CGRP Upregulates TGF-β1 through RAMP1 Signaling during Mechanical Stretch in Kidney Proximal Tubule Epithelial Cells

Moon Daeun (문다은); Babu J. Padanilam; Hee-Seong Jang (장희성); Jinu Kim (김진우)

doi:10.11637/aba.2020.33.4.173

Extraneural CGRP Upregulates TGF-β1 through RAMP1 Signaling during Mechanical Stretch in Kidney Proximal Tubule Epithelial Cells

Anatomy & Biological Anthropology
Abbr : Anat Biol Anthropol
2020, 33(4), pp.173~180
DOI : 10.11637/aba.2020.33.4.173
Publisher : 대한체질인류학회
Research Area : Medicine and Pharmacy > Anatomy
Received : December 4, 2020
Accepted : December 16, 2020
Published : December 31, 2020

Moon Daeun ¹, Babu J. Padanilam ², Hee-Seong Jang ³, Jinu Kim ¹

¹제주대학교
²Department of Cellular and Integrative Physiology, University of Nebraska Medical Center
³University of Nebraska Medical Center, Omaha, NE, USA

Accredited

ABSTRACT

Calcitonin gene-related peptide (CGRP) derived from sensory neurons contributes to the development of renal tubulointerstitial fibrosis during ureteral obstruction through upregulation of profibrotic factors. However, the mechanism by which CGRP upregulates the profibrotic factors in the ureteral obstructive setting in the kidney tubule epithelial cells is not defined. In the human kidney proximal tubule epithelial cell line, HK-2, treatment with 1 nM CGRP significantly enhanced transforming growth factor-β1 (TGF-β1) production, its release, and protein kinase C (PKC) activity. Furthermore, mechanical stretch for 6 and 24 hours significantly increased expressions of receptor activity modifying protein 1 (RAMP1) mRNA and protein among CGRP receptor components in HK-2 cells. In addition, a combination treatment with CGRP and mechanical stretch synergistically increased TGF-β1 upregulation and PKC activation. However, RAMP1 deficiency, induced by RAMP1 double nickase plasmid transfection, abolished CGRP-induced TGF-β1 upregulation and PKC activation in HK-2 cells with or without mechanical stretch. Finally, pharmacological inhibition of PKC markedly reduced TGF-β1 production and release after treatment of HK-2 cells with CGRP. Taken together, these data suggest that extraneural CGRP upregulates TGF-β1 through RAMP1-PKC axis during mechanical stretch in kidney proximal tubule epithelial cells.

KEYWORDS

Fibrosis, Calcitonin gene-related peptide, RAMP1, TGF-β, Protein kinase C

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Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Extraneural CGRP Upregulates TGF-β1 through RAMP1 Signaling during Mechanical Stretch in Kidney Proximal Tubule Epithelial Cells

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Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Extraneural CGRP Upregulates TGF-β1 through RAMP1 Signaling during Mechanical Stretch in Kidney Proximal Tubule Epithelial Cells

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