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Published on: November 10, 2021
Fibroblast Growth Factor 2 Is Produced By Renal Tubular Cells to Act as a Paracrine Factor in Maladaptive Kidney
Xiaoru Hu1, Zhengwei Ma2, Siyao Li1
1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital at Central South University, Changsha, People's Republic of China; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia.
Abstract:
Kidney repair after injury involves the cross-talk of injured kidney tubules with interstitial fibroblasts and immune cells. Although tubular cells produce multiple cytokines, the role and regulation of specific cytokines in kidney repair are largely undefined. In this study, we detected the induction of fibroblast growth factor 2 (FGF2) in mouse kidneys after repeated low-dose cisplatin (RLDC) treatment and in RLDC-treated renal proximal tubule cells in vitro. We further detected FGF2 in the culture medium of RLDC-treated renal tubular cells but not in the medium of control cells, indicating that RLDC induces FGF2 expression and secretion. Compared with the medium of control cells, the medium of RLDC-treated renal tubular cells was twice as effective in promoting fibroblast proliferation. Remarkably, the proliferative effect of the RLDC-treated cell medium was diminished by FGF2-neutralizing antibodies. In addition, the RLDC-treated cell medium induced the expression of fibrosis-related proteins, which was partially suppressed by FGF2-neutralizing antibodies. In mice, FGF2 deficiency partially prevented RLDC-induced decline in kidney function, loss of kidney weight, renal fibrosis, and inflammation. Together, these results indicate that FGF2 is produced by renal tubular cells after kidney injury and acts as an important paracrine factor in maladaptive kidney repair and disease progression.
Insights
Fibroblast growth factor 2 (FGF2) is produced by kidney tubule cells after injury. This factor promotes kidney fibrosis and inflammation, contributing to kidney disease progression.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Kidney repair involves complex cellular interactions, including communication between injured tubules, fibroblasts, and immune cells.
- The precise roles of cytokines produced by tubular cells in kidney repair remain largely unclear.
Purpose of the Study:
- To investigate the role of fibroblast growth factor 2 (FGF2) in kidney repair following injury.
- To determine if FGF2 is induced by kidney injury and if it contributes to maladaptive repair processes.
Main Methods:
- Induction of kidney injury in mice using repeated low-dose cisplatin (RLDC).
- In vitro studies using RLDC-treated renal proximal tubule cells.
- Assessment of FGF2 expression, secretion, and its effects on fibroblast proliferation and fibrosis-related protein expression.
- Evaluation of kidney function, fibrosis, and inflammation in FGF2-deficient mice post-RLDC treatment.
Main Results:
- RLDC treatment induced FGF2 expression and secretion in renal tubular cells.
- RLDC-treated cell medium promoted fibroblast proliferation, an effect dependent on FGF2.
- FGF2 contributed to the induction of fibrosis-related proteins.
- FGF2 deficiency partially protected against RLDC-induced kidney dysfunction, fibrosis, and inflammation.
Conclusions:
- Renal tubular cells produce FGF2 in response to kidney injury.
- FGF2 acts as a paracrine factor that exacerbates kidney fibrosis and inflammation.
- Targeting FGF2 may offer a therapeutic strategy for preventing maladaptive kidney repair and disease progression.
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