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Mechanisms of norcantharidin against renal tubulointerstitial fibrosis

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Abstract

Renal tubulointerstitial fibrosis (RTIF) is a common feature and inevitable consequence of all progressive chronic kidney diseases, leading to end-stage renal failure regardless of the initial cause. Although research over the past few decades has greatly improved our understanding of the pathophysiology of RTIF, until now there has been no specific treatment available that can halt the progression of RTIF. Norcantharidin (NCTD) is a demethylated analogue of cantharidin, a natural compound isolated from 1500 species of medicinal insect, the blister beetle (Mylabris phalerata Pallas), traditionally used for medicinal purposes. Many studies have found that NCTD can attenuate RTIF and has the potential to be an anti-RTIF drug. This article reviews the recent progress of NCTD in the treatment of RTIF, with emphasis on the pharmacological mechanism of NCTD against RTIF.

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Abbreviations

α-SMA:

α-Smooth muscle actin

BMP:

Bone morphogenetic protein

BSA:

Bovine serum albumin

CaN:

Calcineurin

CDKN1A:

Cyclin-dependent kinase inhibitor 1A

CKDs:

Chronic kidney diseases

Col-I:

Collagen I

Col IV:

Type IV Collagen

CRF:

Chronic renal failure

CTD:

Cantharidin

CTGF:

Connective tissue growth factor or CCN2

DN:

Diabetic nephropathy

ECM:

Extracellular matrix

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

EZH2:

Zeste homolog 2

FN:

Fibronectin, a fibrosis marker

Fn14:

Fibroblast growth factor-inducible 14

FoxO:

Forkhead box O

GAS5:

Growth arrest-specific transcript 5

H3 K79:

Histone H3 lysine79

HEA:

N6-(2-Hydroxyethyl) adenosine

HK-2 cells:

Human renal proximal tubular epithelial cell line

ITGB1:

Integrin beta-1

JNK:

C-Jun amino terminal kinase

KLF5:

Krüppel- like factor 5

lncRNAs:

Long noncoding RNA molecules

miRNAs:

MicroRNAs

MMP9:

Matrix metalloproteinase 9

ncRNAs:

Non-coding RNAs

NCTD:

Norcantharidin

NF-κB:

Nuclear factor-kappaB

NFATc:

Nuclear factor of activated T cells cytosolic component

Nrf2:

Nuclear factor erythroid2-related factor2

OA:

Okadaic acid

PAI-1:

Plasminogen activator inhibitor-1 or SERPINE1

Pink1:

PTEN-induced kinase 1

PON:

Protein overload nephropathy

PP2A:

Protein phosphatase 2A

PP2Aa:

A structural subunit A of PP2A

PP2Ab:

A highly variable regulatory subunit B of PP2A

PP2Ac:

A catalytic subunit C of PP2A

p-Smad3:

C-terminal-phosphorylated Smad3

RTIF:

Renal tubulointerstitial fibrosis

SHH:

Sonic Hedgehog

SIS3:

A specific inhibitor of Smad3

Smad:

Mothers against decapentaplegic homolog

Snail1:

A transcription factor of E-cadherin

SncRNAs:

Short ncRNAs

Sp1:

Special protein1

STAT3:

Signal transducer and activator of transcription 3

TGF-β1:

Transforming growth factor-β1

TWEAK:

Tumor necrosis factor-like weak inducer of apoptosis

UUO:

Unilateral ureteral obstruction

XIST:

X-inactive specific transcript

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Funding

This work was supported by National Natural Science Foundation of China (NSFC82003702) and Shanghai-Sailing Program (no. 21YF1438000).

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Authors and Affiliations

  1. Department of Pharmacy, The First People’s Hospital of Changzhou and the 3rd Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, Jiangsu, China

    Qin-Su Yun

  2. Research Center for Medicine and Biology, Zunyi Medical University, 6 West Xuefu Road, Zunyi, 563000, Guizhou, China

    Yu-Xin Bao

  3. Department of Pharmacology, Naval Medical University, Shanghai, 200433, China

    Jie-Bing Jiang

  4. Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University, 881 Yonghe Road, Nantong, 226001 , Jiangsu, China

    Qian Guo

  5. Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 99 Shangda Road, Shanghai, 200444, China

    Qian Guo

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Writing—original draft preparation: QSY, JBJ and QG; writing—review and editing: QG; supervision, QG; funding acquisition: QG; project administration: QG and YXB. All authors read and agreed to the published version of the manuscript.

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Yun, QS., Bao, YX., Jiang, JB. et al. Mechanisms of norcantharidin against renal tubulointerstitial fibrosis. Pharmacol. Rep 76, 263–272 (2024). https://doi.org/10.1007/s43440-024-00578-5

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