Acute-phase response protein serum amyloid A stimulates renal tubule formation: studies in vitro and in vivo

Abstract

Kelly KJ, Kluve-Beckerman B, Dominguez JH. Acute-phase response protein serum amyloid A stimulates renal tubule formation: studies in vitro and in vivo.

IL-22 Induces an Acute-Phase Response

“…With regard to intestinal homeostasis, Ivanov et al (51) SAA is also able to induce renal tubule formation in vitro with the in vivo expression of SAA associated with tubule generation in embryonic or ischemic kidneys (52). We demonstrate that sustained IL-22 exposure, delivered by adenovirus (Fig.…”

Intravenous cell therapy for acute renal failure with serum amyloid A protein-reprogrammed cells

“…Current work has demonstrated a strong renal inflammatory component following AKI (14), and some have reported that mediators of inflammation could also be beneficial in AKI (4). The notion that components of inflammation can be protective is supported by our work showing that serum amyloid A protein (SAA), a classic component of the acutephase reaction linked to inflammation, also promotes tubulogenesis (15). With the availability of bone marrow-derived stem cells, infusion of exogenous potential renal cell precursors became possible, and attempts have been made to replace and renew the damaged renal cell populations.…”

“…Thus the benefit from stem cell infusions was thought to be secondary to a paracrine action rather than structural replacement by a cell population of exogenous origin (2,26). In this work, we report that NRK52E cells reprogrammed to express tubulogenic mouse SAA1.1 (15) formed tubules in vitro and promoted recovery when these reprogrammed cells were injected into rats with AKI.…”

“…Paraformaldehyde-fixed cells were incubated overnight with primary antibodies: rabbit anti-SAA1.1 (1: 1,000) manufactured in our laboratory (15), rabbit anti-organic anion transporter 1 (OAT1; affinity-purified IgG) used at a concentration of 6.5 g/ml (catalog no. OAT11-A; Alpha Diagnostic International, San Antonio, TX), and rabbit anti-rat sodium/hydrogen exchanger 3 (NHE3; affinity-purified IgG) used at a concentration of 20 g/ml (catalog no.…”

“…Cells were rinsed in PBS and labeled with Texas red-conjugated goat anti-rabbit IgG (1:200, Jackson ImmunoResearch, West Grove, PA) for 1 h and the nuclear dye 4,6-diamidino-2-phenylindole (Molecular Probes, Eugene, OR) for 20 min. The cells were rinsed with PBS and imaged with a Zeiss LSM 510 confocal microscope equipped with UV, argon, and helium lasers (15). Apoptotic cells in culture and in kidney sections were identified as those with condensed, fragmented nuclei and expressed as the fraction of total nuclei in the image (14).…”