The role of autophagy in unilateral ureteral obstruction rat model

Kim, Wan-Young; Nam, Sun Ah; Song, Ho Cheol; Ko, Jun Sung; Park, Sang Hee; Kim, Hong Lim; Choi, Euy Jin; Kim, Yong Soo; Kim, Jin; Kim, Yong Kyun

doi:10.1111/j.1440-1797.2011.01541.x

Cited by 98 publications

(109 citation statements)

References 23 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…30 This is in sharp contrast with our current observations, which indicate that inhibition of autophagy pharmacologically or genetically decreased tubular cell apoptosis and diminished interstitial fibrosis in the mouse model of UUO (Figs. 3, 6A and 6B).…”

Section: Discussioncontrasting

confidence: 57%

“…[28][29][30][31][32]35 Using pharmacological and genetic inhibitory approaches, our study has determined the regulation of renal interstitial fibrosis by autophagy in the in vivo model of UUO and in vitro model of TGFB1-treated proximal tubular cells. The results show that blockade of autophagy by pharmacological inhibitors (choloroquine and 3-methyladenine) or conditional Atg7 deletion from proximal tubules suppressed renal interstitial fibrosis during UUO.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30][31][32] The techniques for analyzing autophagy in vivo in those studies mainly include electron microscopy profile of autophagic vesicles, immunohistochemical staining of LC3, GFP-LC3 fluorescent puncta, and conversion of LC3-I to LC3-II. These methods can monitor autophagy at steady-state levels, but they do not reveal the dynamic nature of autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…30 To address this discrepancy and further define the role of tubular autophagy in kidney fibrosis, we employed a conditional knockout mouse model with Atg7 specifically deleted from renal proximal tubules (PT-Atg7 KO). This model was recently generated by our lab and demonstrated autophagy defects in proximal tubules in nephrotoxic and ischemic models of AKI.…”

Section: Autophagy Is Persistently Induced In Kidney Proximal Tubulesmentioning

confidence: 99%

“…23 In the kidney, autophagy appears to occur in the UUO model of kidney fibrosis. [28][29][30][31][32] Also, TGFB1 activates autophagy in renal tubules in mice and in cultured renal tubular and mesangial cells. [33][34][35] Under these conditions, however, the role(s) of autophagy in renal interstitial fibrosis is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

et al. 2016

View full text Add to dashboard Cite

Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUOassociated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/a-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor b 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors.

show abstract

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Autophagy Is Persistently Induced In Kidney Proximal Tubulesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

et al. 2016

View full text Add to dashboard Cite

show abstract

LncRNA CCAT1 functions as apoptosis inhibitor in podocytes via autophagy inhibition

Yao

Zhao

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Podocyte apoptosis importantly contributes to various kidney diseases. Long noncoding RNAs Colon cancer‐associated transcript‐1 (CCAT‐1) has been demonstrated for a critical role in cell proliferation. In the present study, the relationship between CCAT1 and popdocyte impairment, and the underlying mechanism was investigated. Podocytes were isolated from mice and then treated with tumor necrosis factor‐α to simulate podocyte injury. After developed CCAT1 overexpression or knockdown, cell viabilities were determined with the CCK‐8 assay, apoptosis was examined with Flow cytometry, the autophagy was observed by Western blot. Furthermore, phosphorylated PI3K and Akt expressions were examined. We found that after CCAT1 overexpression, the cell viability was significantly increased, apoptosis was significantly decreased, and autophagy was significantly inhibited, which was indicated by induced P62, LC3B‐I and decreased LC3B‐II. In addition, CCAT1 overexpression induced the levels of phosphorylated PI3K and Akt. With Rap treatment, these effects by CCAT1 were reversed. Furthermore, the results contrary to the effects by CCAT1 overexpression were presented after CCAT1 knockdown, and this was inhibited by 3‐MA. Taken together, our results suggested that CCAT1 induction critically participated in apoptosis inhibition in podocytes through autophagy inhibition via increasing PI3K/Akt signaling. This might act as a promising therapeutic intervention for renal diseases associated with podocyte apoptosis.

show abstract

LncRNA ENST00000453774.1 contributes to oxidative stress defense dependent on autophagy mediation to reduce extracellular matrix and alleviate renal fibrosis

Xiao

Yuan

Chen

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Although long noncoding RNA (LncRNA) are important players in the initiation and progression of many pathological processes, the role of LncRNAENST00000453774.1 (LncRNA 74.1) in renal fibrosis still remains unclear. Lentivirus mediated LncRNA 74.1 overexpressing HK2 cells and overexpression mice models were constructed. HK2 cells induced by transforming growth factor‐β (TGF‐β) in vitro, and the mice UUO model in vivo were used to simulate renal fibrosis. The expression of LncRNA 74.1 was significantly downregulated in the TGF‐β‐induced HK‐2 cell fibrosis and clinical renal fibrosis specimens. LncRNA 74.1 overexpression obviously attenuated renal fibrosis in vitro and unilateral ureteral obstruction‐induced renal fibrosis in vivo. LncRNA 74.1 promoted reactive oxygen species defense by activating prosurvival autophagy then decreased ECM‐related proteins fibronectin and collagen I involved in renal fibrosis. We also found that Nrf2‐keap1 signaling played important roles in the remission of ECM mediated by LncRNA 74.1. This study indicates that LncRNA 74.1 downregulation would contribute to renal fibrosis and its overexpression might represent a novel anti‐fibrotic treatment in renal diseases.

show abstract

The role of autophagy in unilateral ureteral obstruction rat model

Abstract: Our present results support that autophagy induced by UUO has a renoprotective role in the obstructed kidney and regulatory role of compensatory cellular proliferation in the contralateral kidney through Akt-mTOR signalling pathway.

Cited by 98 publications

References 23 publications

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction

LncRNA CCAT1 functions as apoptosis inhibitor in podocytes via autophagy inhibition

LncRNA ENST00000453774.1 contributes to oxidative stress defense dependent on autophagy mediation to reduce extracellular matrix and alleviate renal fibrosis

Contact Info

Product

Resources

About