The roles of pyroptosis in genitourinary diseases

Abstract

Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with the pathogenesis of diseases. Recently, the association between pyroptosis and urinary diseases has attracted considerable attention, and a comprehensive review focusing on this issue is not available. In this study, we reviewed the role of pyroptosis in the development and progression of benign urinary diseases and urinary malignancies. Based on this, pyroptosis has been implicated in the development of urinary diseases. In summary, this review sheds light on future research directions and provides novel ideas for using pyroptosis as a powerful tool to fight urinary diseases.

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International Urology and Nephrology (2024) 56:1515–1523
https://doi.org/10.1007/s11255-023-03894-6
UROLOGY - REVIEW
The roles ofpyroptosis ingenitourinary diseases
HaopengLiu1· HaoranLiu1· GuoshuaiHuang1· HexingYuan1· XuefengZhang1
Received: 2 September 2023 / Accepted: 15 November 2023 / Published online: 16 December 2023
© The Author(s) 2023
Abstract
Pyroptosis, a form of programmed cell death distinct from apoptosis and necrosis, is thought to be closely associated with
the pathogenesis of diseases. Recently, the association between pyroptosis and urinary diseases has attracted considerable
attention, and a comprehensive review focusing on this issue is not available. In this study, we reviewed the role of pyropto-
sis in the development and progression of benign urinary diseases and urinary malignancies. Based on this, pyroptosis has
been implicated in the development of urinary diseases. In summary, this review sheds light on future research directions
and provides novel ideas for using pyroptosis as a powerful tool to fight urinary diseases.
Keywords Pyroptosis· Regulated cell death· Genitourinary diseases· Mechanism· Gasdermins
Abbreviations
ASC Caspase-recruitment domain
ROS Reactive oxygen species
IL-18 Interleukin-18
IL-1β Interleukin-1β
LPS Lipopolysaccharide
TAK1 TGF-β-activated kinase-1
GSDMA Gasdermin A
GSDMB Gasdermin B
GSDMC Gasdermin C
GSDMD Gasdermin D
GSDME Gasdermin E
GZMB Granzyme B
GZMA Granzyme A
USF2 Upstream stimulatory factor 2
THBS1 Thrombospondin-1
NLRP1 NOD-like receptor 1
AIM2 Absent in melanoma 2
NLRP3 NOD-like receptor 3
HMGB1 High mobility group box1
ERS Endoplasmic reticulum stress
TLR2 Toll-like receptor 2
ROCK1 Rho-associated coiled-coil containing protein
kinase-1
TXNIP Thioredoxin–interacting protein
miR-93 MicroRNA-93
PRDX3 Peroxiredoxin 3
STAT3 Transcription 3
HK2 Hexokinase 2
LDHA Lactate dehydrogenase A
ENO2 Enolase 2
USP24 Ubiquitin-specific peptidase 24
IGFBP3 Insulin-like growth factor-binding protein 3
Introduction
Pyroptosis is a newly discovered form of programmed cell
death. Cell death is usually categorized as nonprogrammed
cell death and programmed cell death (PCD) [1]. Pyroptosis
is a type of inflammatory PCD [2]. The process of pyrop-
tosis was first described in 1992, but the term was coined
in 2001 following the observation that bacterium-infected
macrophages underwent rapid lytic cell death dependent on
caspase-1 activity [3]. Recently, macrophages were shown to
regulate pyroptosis and play an important role in the devel-
opment of acute kidney injury (AKI), diabetic nephropathy
(DN) and renal fibrosis [4–6]. Pyroptosis is characterized
by cell membrane pore formation, cell swelling, and the
release of inflammatory intracellular contents [7, 8]. The
inflammatory factors released during cell lysis, such as
interleukin-1β (IL-1β) and interleukin-18 (IL-18), amplify
* Hexing Yuan
yuanhexing@suda.edu.cn
* Xuefeng Zhang
zhangxuefeng626@sina.com
1 Department ofUrology, The First Affiliated Hospital
ofSoochow University, 188 Shizi Road, Suzhou, China
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1516 International Urology and Nephrology (2024) 56:1515–1523
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the inflammatory effects and activate immune responses [7,
8].
The underlying mechanism was only uncovered upon
the discovery of gasdermin D (GSDMD) protein. Shi etal.
found that caspase-1/11/4/5 can induce pyroptosis by cleav-
ing GSDMD to release its N-terminal domain [9]. In addi-
tion to GSDMD, the gasdermin family also includes five
other members. The human gasdermin family comprises
GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DFNA5,
and PVJK/DFNB59. In mice, there are five gasdermin mem-
bers, namely, GSDMA, GSDMC, GSDMD, GSDME, and
PJVK/DFNB59, but not GSDMB [2]. All gasdermins except
DFNB59 have two conserved domains: an N-terminal effec-
tor domain and a C-terminal inhibitory domain [2].
Normally, moderate pyroptosis contributes to host
defence against pathogen infection, but excessive pyropto-
sis leads to uncontrolled inflammatory responses, massive
cell death, and serious tissue damage, causing inflammatory
or autoimmune diseases [2]. As a proinflammatory type of
cell death, pyroptosis provides a new opportunity for cancer
elimination by activating the anti-tumour immune response
[2]. An increasing number of studies have shown that pyrop-
tosis plays a crucial role in many cancers, such as breast
cancer, gastric cancer, and lung cancer [10–12].
Here, we first describe the different signalling path-
ways of pyroptosis to gain an in-depth understanding of
the molecular mechanism. Finally, the role of pyroptosis in
urinary diseases is discussed, followed by suggestions for
future research directions.
Overview ofpyroptosis
Canonical pathway
The classical pyroptosis pathway is mediated by caspase-1
[13]. Inflammasomes are formed by pattern-recognition
receptors (PRRs, also known as inflammasome sensors),
apoptosis-associated speck-like protein containing a cas-
pase-recruitment domain (ASC), and inactive pro-caspase-1
[13–15]. PRRs can recognize pathogen-associated molecular
patterns and danger-associated molecular patterns (PAMPs
and DAMPs) [16, 17]. PRRs include nucleotide-binding
oligomerization domain-like receptors (NLRs, includ-
ing NLRP1, NLRP3, and NLRC4), absent in melanoma
2 (AIM2), and pyrin [18, 19]. NLRs usually consist of a
leucine-rich repeat (LRR), a nucleotide-binding oligomeri-
zation domain (NACHT/NOD), and a caspase-recruitment
domain (CARD) or pyrin domain (PYD) and are divided
into NLRPs or NLRCs according to whether their N-termi-
nus contains a PYD or CARD [20]. A PYD is needed for
interaction with ASC. The NOD participates in adenosine
triphosphate (ATP)-dependent activation of the signal. The
LRR is responsible for ligand recognition and autoinhibi-
tion. The CARD participates in pro-caspase-1 recruitment
[2]. Upon receiving an activating signal, inflammasome
sensors recruit pro-caspase-1 (which has a CARD) either
directly through homotypic binding of CARD or indirectly
through the PYD by means of ASC, which contains a PYD
and a CARD [17]. Subsequently, caspase-1 activation
occurs through self-cleavage. Activated caspase-1 not only
cleaves inactive IL-1β and IL-18 precursors but also cleaves
GSDMD to form GSDMD-NT and GSDMD-CT [21–24].
GSDMD-N forms pores in the plasma membrane, leading
to cell swelling and pyroptosis [25, 26] (Fig.1).
Non‑canonical pathway
Most gram-negative bacteria activate the non-canonical
inflammasome pathway [2]. The nonclassical signalling
pathway is mediated by caspase-4 and caspase-5 in humans
and by caspase-11 in mice [27, 28]. These caspases can be
activated by directly binding to lipopolysaccharide (LPS)
[28]. Activated caspase-4/5/11 cleaves GSDMD to promote
pyroptosis. However, caspase-4/5/11 cannot cleave pro-
IL-18/pro-IL-1β but can cleave GSDMD, which can cause
K+ efflux and NLRP3/caspase-1 pathway activation, eventu-
ally leading to the maturation and release of interleukin-18
(IL-18) and interleukin-1β (IL-1β) [9, 14, 29] (Fig.1).
Apoptotic caspase‑mediated pathway
In addition to inflammatory caspase-1/4/5/11, some apop-
totic caspases can also trigger pyroptosis. Chemotherapeu-
tic drugs can induce caspase-3 to cleave GSDME to form
GSDME-N termini, which cause pyroptosis [30, 31]. In
addition, pathogenic Yersinia has been shown to inhibit
TGFβ-activated kinase-1 (TAK1) via the Yersinia effec-
tor protein YopJ and induce caspase-8-related cleavage of
GSDMD to elicit pyroptosis [32, 33]. Interestingly, cas-
pase-8 induces GSDMC cleavage, thereby leading to a non-
canonical pyroptosis pathway in cancer cells [34] (Fig.1).
Granzyme‑mediated pathway
Granzyme A (GzmA) is the most abundant serine protease
of the granzyme family and has traditionally been recog-
nized as a mediator of cell death [2]. Zhou etal. found
that GZMA derived from cytotoxic T lymphocytes cleaves
GSDMB to induce pyroptosis [35]. In 2020, it was reported
that CAR-T cells activated caspase-3 by releasing granzyme
B (GzmB), subsequently leading to the activation of the cas-
pase-3/GSDME-mediated pyroptotic pathway, thus causing
pyroptosis [36]. Additionally, Zhang etal. found that GzmB
directly cleaved GSDME and induced pyroptosis, enhancing
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1517International Urology and Nephrology (2024) 56:1515–1523
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anti-tumour immunity and inhibiting tumour growth [37]
(Fig.1).
Pyroptosis inbenign urinary diseases
Pyroptosis ininterstitial cystitis
Interstitial cystitis (IC), also known as bladder pain syn-
drome (BPS), is a chronic pain disorder that most commonly
presents in the bladder, pelvis, or abdomen [38]. Pyroptosis
plays an important role in the development of IC. A study
showed that the NLRP3 inflammasome is a crucial player
in the development of bladder disease [39]. Some results
have demonstrated that the expression levels of NLRP3, cas-
pase-1, and GSDMD in patients with IC are elevated [40,
41]. Wang etal. found that the NLRP3/GSDMD-N pathway
was activated and played a role in the development of IC
[42]. Wang etal. showed that aster tataricus extract (ATE)
can be used as an inhibitor of NLRP3 in treating IC [43].
The discovery of NLRP3/caspase-1/GSDMD-N as a new
pathway provides a new direction for IC research.
Pyroptosis inBPH
Benign prostatic hyperplasia (BPH) is characterized by the
nonmalignant overgrowth of prostatic tissue surrounding the
urethra, ultimately constricting the urethral opening and giv-
ing rise to associated lower urinary tract symptoms (LUTS)
such as urgency, frequency, nocturia, incomplete bladder
emptying, and a weak urine stream [44]. There is much
evidence to suggest that inflammation plays an important
role in BPH. It has been reported that the expression lev-
els of NLRP1 and caspase-1, IL-18 and IL-1β are elevated
in BPH [45]. Therefore, the NLRP1/caspase-1 pathway
is activated and participates in the development of BPH.
Fig. 1 Molecular mechanisms of the canonical pathway, non-canon-
ical pathway, apoptotic caspase-mediated pathway and granzyme-
mediated pathway in pyroptosis. In the canonical pathway, patho-
gen-associated molecular patterns or damage-associated molecular
patterns (such as ROS, ATP, viruses, bacteria, or toxins) stimulate
inflammasomes, which then activate caspase-1. Activated cas-
pase-1 not only cleaves inactive IL-1β and IL-18 precursors but also
cleaves GSDMD, which forms pores and induces pyroptosis. In the
non-canonical pathway, LPS from Gram-negative bacteria activates
caspase-4/5/11, and activated caspase-4/5/11 cleaves GSDMD to
promote pyroptosis. In the apoptotic caspase-mediated pathway, cas-
pase-3/GSDME, caspase-8/GSDMD and caspase-8/GSDMC mecha-
nisms can promote pyroptosis. In the granzyme-mediated pathway,
GZMA or GZMB derived from CAR-T cells cleaves GSDMB or
GSDME, respectively, to induce pyroptosis. ASC caspase-recruit-
ment domain, ROS reactive oxygen species, IL-18 interleukin-18,
IL-1β interleukin-1β, LPS lipopolysaccharide, TAKI TGF-β-activated
kinase-1, GSDMD gasdermin D, GSDME gasdermin E, GSDMB gas-
dermin B, GZMB granzyme B, GZMA granzyme A
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Jiang etal. found that peroxiredoxin 3 (PRDX3) suppressed
autophagy flux and activated pyroptosis to induce inflam-
matory responses and stimulate the overgrowth of prostate
tissues [46]. Emerging results indicate that steady-state
levels of AIM2 mRNA are higher in BPH tissue than in
normal prostate tissue [47]. AIM2 recruits ASC and pro-
caspase-1 to assemble the AIM2 inflammasome, leading to
cell swelling and pyroptosis. These studies have facilitated
the identification of potential BPH treatment targets. The
signalling pathways regulating pyroptosis in BPH are dis-
played in Fig.3.
Pyroptosis inAKI
Acute kidney injury (AKI) is defined by a rapid increase
in serum creatinine, a decrease in urine output, or both
[48]. Recent advances have revealed a role for pyroptosis in
AKI. Sun etal. found that thrombospondin-1 (THBS1) and
upstream stimulatory factor 2 (USF2) were highly expressed
in patients with sepsis-induced AKI and that USF2 upregu-
lated THBS1 expression to activate the TGF-β/Smad3/
NLRP3/caspase-1 signalling pathway and stimulate pyrop-
tosis, ultimately exacerbating sepsis-induced AKI [49]. Miao
etal. found that the expression of GSDMD was significantly
increased in both cisplatin-induced and ischaemia‒reper-
fusion (I/R) models [50]. The knockout of caspase-11 or
GSDMD alleviated kidney damage in mice with cisplatin-
induced AKI. A study published in 2020 showed that the
protein levels of high mobility group box1 (HMGB1),
IL-1β, IL-18, NLRP3, and GSDMD were elevated in an
AKI model [6]. Therefore, we hypothesize that the HMGB1/
NLRP3/GSDMD signalling pathway plays a pivotal role in
the pathogenesis of AKI. In addition, Li etal. demonstrated
that the ROS/NLRP3/caspase-1/GSDMD pathway medi-
ated contrast-induced AKI (CI-AKI) via pyroptosis and
that baicalin treatment alleviated the associated inflamma-
tion and oxidation levels [51]. Studies have also shown that
macrophage-derived exosomal miRNAs play important roles
in AKI [52, 53]. Xia etal. found that the levels of GSDME-
N and IL-1β were elevated in cisplatin-induced AKI [54].
The inhibition of caspase-3 blocked GSDME-N cleavage
and attenuated cisplatin-induced pyroptosis and kidney dys-
function. Therefore, caspase-3/GSDME-triggered pyroptosis
plays an important role in AKI. Juan etal. found that the
exosomal miR-93/thioredoxin–interacting protein (TXNIP)
signalling pathway plays a crucial role in the progression of
sepsis-induced AKI and that M1 exosomes promote pyrop-
tosis and M2 exosomes inhibit pyroptosis [55]. It has been
well established that Rho-associated coiled-coil containing
protein kinase-1 (ROCK1) plays an important role in a series
of pathological processes, including pyroptosis, inflamma-
tion, and endoplasmic reticulum stress (ERS) [56, 57]. Wang
etal. found that ROCK1 regulates LPS-induced kidney cell
pyroptosis via Toll-like receptor 2 (TLR2)-mediated ERS,
thereby accelerating sepsis-induced AKI progression [58].
The signalling pathways regulating pyroptosis in AKI are
displayed in Fig.2.
Pyroptosis inDN
Diabetic nephropathy (DN), or diabetic kidney disease
(DKD), is a frequent and severe long-term microvascular
complication resulting from lesions in the renal glomeruli
and tubules [59]. Growing evidence has demonstrated that
chronic inflammation promotes the pathogenesis of DN
[60]. The role of pyroptosis signalling pathways in DN
progression has attracted the attention of researchers and
clinicians. In 2020, it was reported that the TXNIP/NLRP3
axis is an important pathway that regulates DN induced by
pyroptosis [61]. Interestingly, Ke etal. found that the ERS-
related factor IRE1α upregulated TXNIP/NLRP3 inflamma-
some-induced pyroptosis in DN rats [62]. Li etal. found
that NLRP3/caspase-1/GSDMD signalling was strikingly
upregulated and the secretion of IL-1β and IL-18 dramati-
cally increased in DN mice [63]; in addition, they also con-
firmed that SYR inhibited the NLRP3/caspase-1/GSDMD
pyroptosis pathway by upregulating NRF2 signalling in
DN. Li etal. found that the expression of p-NF-κB, ASC,
cleaved-IL-1β, NLRP3, cleaved-caspase-1, and GSDMD-N
was elevated in a DN mouse model [64]; in addition, they
confirmed that geniposide (GE) may inhibit the develop-
ment of DN via the APMK/SIRT1/NF-κB pathway [64].
The APMK/SIRT1/NF-κB axis may become a new signal-
ling pathway for the treatment of DN. In addition, NLRP3
inflammasome activation is related to the pathogenesis of
DN. Wang etal. revealed that the expression of NLRC4,
IL-1β, and IL-18 was increased under high glucose condi-
tions, inducing pyroptosis in renal tubular epithelial cells
[65]. Komada etal. demonstrated that the activation of the
AIM2 inflammasome by DNA from necrotic cells drives
pyroptosis, which contributes to chronic kidney injury [66].
Cheng etal. demonstrated that caspase-11/4- and GSDMD-
mediated pyroptosis was activated in a DN mouse model
and involved in the development of DN [67]. In summary,
these findings confirm that pyroptosis and inflammasomes
play important roles in renal injury, ultimately affecting the
pathogenesis of DN.
Pyroptosis inurinary malignancies
Pyroptosis inbladder cancer
Bladder cancer (BCa) is the most common malignancy of
the urinary tract [68]. Recent advances have revealed an
important role of pyroptosis in bladder cancer. He etal.
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1519International Urology and Nephrology (2024) 56:1515–1523
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found that GSDMB binds to signal transducer and activator
of transcription 3 (STAT3) and increases the phosphoryla-
tion of STAT3, which increases the expression of hexoki-
nase 2 (HK2), lactate dehydrogenase A (LDHA), enolase
2 (ENO2), and insulin-like growth factor-binding protein 3
(IGFBP3) to enhance glycolysis in BCa cells and promote
cancer cell proliferation [69]; in addition, they also demon-
strated that ubiquitin-specific peptidase 24 (USP24) inter-
acts with GSDMB and prevents GSDMB degradation in
BCa cells [69]. Therefore, the USP24/GSDMB/STAT3 axis
may become a new targetable signalling pathway for blad-
der cancer treatment. Chen etal. showed, based on K‒M
Fig. 2 Signalling pathways regulating pyroptosis in AKI. THBS1
is upregulated by USF2 and activates the TGF-β/Smad3/NLRP3/
caspase-1 signalling pathway, thus inducing pyroptosis. NLRP3 is
upregulated by HMGB1 and activates the expression of GSDMD.
ROS induce pyroptosis via the NLRP3/caspase-1/GSDMD signalling
axis. Cisplatin induces pyroptosis via the caspase-3/GSDME signal
axis. miR-93 targets TXN2P and thus induces pyroptosis. ROCK1
regulates LPS-induced pyroptosis via TLR2-mediated ERS. USF2
upstream stimulatory factor 2, ROS reactive oxygen species, THBS1
thrombospondin-1, TGF-β transforming growth factor-β, NLRP3
NOD-like receptor 3, HMGB1 high mobility group box 1, LPS
lipopolysaccharide, ERS endoplasmic reticulum stress, TLR2 toll-
like receptor 2, ROCK1 Rho-associated coiled-coil containing pro-
tein kinase-1, TXNIP thioredoxin–interacting protein, miR-93 micro-
RNA-93, GSDMD gasdermin D, GSDME gasdermin E
Fig. 3 Signalling pathways
regulating pyroptosis in BPH.
NLRP1/caspase-1 induces
pyroptosis to promote the
development of BPH. PRDX3
suppresses autophagy flux
and activates pyroptosis to
promote the development of
BPH. AIM2/caspase-1 induces
pyroptosis to promote the
development of BPH. PRDX3
peroxiredoxin 3, NLRP1 NOD-
like receptor 1, AIM2 absent
in melanoma 2, BPH benign
prostatic hyperplasia
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1520 International Urology and Nephrology (2024) 56:1515–1523
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curves, that GSDMB and CASP6 are associated with better
prognoses for patients with BCa [70]; they also found that
many tumours with high GSDMB and CASP6 expression
were immune-inflamed tumours and that many tumours with
low GSDMB and CASP6 expression were immune-desert
tumours. Then, they demonstrated that GSDMB and CASP6
play important roles in immune infiltration [70]. The results
from El-Gamal etal. showed that the expression level of
GSDMD in muscle-invasive bladder cancer (MIBC) was sig-
nificantly higher than that in non-muscle-invasive bladder
cancer (NMIBC) and that the expression level in NMIBC
was higher than that in the control group [71]. These results
show that GSDMD is involved in the pathogenesis of BCa
and muscle invasion. In addition, the expression of GSDMD
in tissue can be used as a useful tool for predicting local
tumour recurrence [71]. Peng etal. found that CD147 pro-
moted cell proliferation in BCa by upregulating the expres-
sion of GSDMD [72].
Pyroptosis inprostate cancer
Prostate cancer (PCa) is a major disease that affects men’s
health worldwide. It is the second most common form of
cancer in men, surpassed only by nonmelanoma skin cancers
such as basal and squamous cell carcinomas [73]. Pyroptosis
is also involved in PCa development. As a classical pyropto-
sis pathway, the caspase-1 pathway plays an important role
in PCa. NLRP3 participates in physiological and pathologi-
cal processes, including tumour progression. In 2021, Xu
etal. found that the expression of NLRP3 in PCa tissues
and cell lines was elevated and was positively correlated
with that of caspase-1 [74]. Their results revealed that the
NLRP3 inflammasome exerted a tumour-promoting effect by
activating caspase-1 in PCa [74]. Karan etal. reported that
the expression of NLRP12 was significantly higher in PCa
tissue than in adjacent benign tissue and that NLRP12 may
play an important role in activating NF-κB and IL-1β signal-
ling and its association with the pathogenesis and progres-
sion of PCa [75]; they indicated that NLRP12 can upregu-
late caspase-1, IL-1 β, and IL-18 to promote the occurrence
and progression of PCa. Many studies have shown that LPS
participates in the proliferation, migration, and invasion of
PCa cells [76–78]. It has been shown that LPS activates the
caspase-4/5/11 pathway to induce pyroptosis [28]. However,
LPS-mediated pyroptosis is still being investigated in PCa.
Pyroptosis inrenal cell carcinoma
Renal cell carcinoma (RCC) accounts for 2–3% of all malig-
nant diseases in adults [79]. It is the seventh most com-
mon cancer in men and the ninth most common in women
[79]. The most common RCC is clear cell RCC (ccRCC)
(70–90%), followed by papillary RCC (10–15%) and
chromophobe RCC (3–5%) [80]. In recent years, research-
ers have found that pyroptosis is inextricably linked to the
development of RCC. Cui etal. found that GSDMB expres-
sion was significantly more upregulated in ccRCC tissues
than in surrounding normal tissues [81]; in addition, they
confirmed that the upregulation of GSDMB is significantly
related to immune infiltrates and poor survival in ccRCC
[81]. GSDMB has the potential to become a biomarker for
poor prognosis and a potential target for immune therapy
in ccRCC. Liver X receptors [LXRs; nuclear receptor
subfamily 1, group H, member 2 (NR1H2, also known as
LXRB) and nuclear receptor subfamily 1, group H, member
3 (NR1H3, also known as LXRA)] belong to the nuclear
receptor superfamily and are expressed in various cells [82].
Wang etal. found that the expression levels of NLRP3 in
ccRCC tissue were significantly lower than those in normal
kidney tissue and that LXRα promoted tumour metastasis
by downregulating the NLRP3 inflammasome in ccRCC
[83]. In addition, bromodomain-containing 4 (BRD4) inhi-
bition was shown to prevent cell proliferation and epithe-
lial–mesenchymal transition (EMT) and play an anti-tumour
role in RCC by activating the NF-κB–NLRP3–caspase-1
pyroptosis signalling pathway [84]. Zhang etal. found that
the expression of most pyroptosis regulatory genes is posi-
tively correlated and plays an important prognostic role in
ccRCC [85]. AIM2 plays a crucial role in the development
of various tumours. Recent studies have shown that AIM2 is
highly expressed in ccRCC and promotes tumour develop-
ment through immune activation pathways [86]. Tang etal.
found that lncRNA FOXD2 adjacent opposite strand RNA
1 (FOXD2-AS1) affects GSDMB and NLRP1 [87]; interest-
ingly, they also found that downregulating the expression
of FOXD2-AS1 reduced the proliferation and migration of
ccRCC cells [87]. This indicates that FOXD2-AS1 may pro-
vide a new direction for research on the treatment of RCC.
Conclusion
In conclusion, pyroptosis is a newly identified form of cell
death mediated by gasdermin proteins, which are often
activated by caspases. It plays a crucial role in the occur-
rence, development, and progression of urologic diseases.
The molecular mechanism of pyroptosis is shown in Fig.1.
The signalling pathways regulating pyroptosis in AKI
are shown in Fig.2. The signalling pathways regulating
pyroptosis in BPH are shown in Fig.3. Future in-depth
research on pyroptosis in urological diseases will help us
better understand the diagnosis and treatment of urinary
diseases. Future studies are urgently needed to develop
more clinical trials to explore the potential application of
pyroptosis in urinary diseases.
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1521International Urology and Nephrology (2024) 56:1515–1523
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Acknowledgements The authors would like to thank their families
for their constant support and encouragement throughout this review.
Author contributions HL, HY, and XZ conceived the study and drafted
the article. HL was a major contributor in writing the manuscript.
HL and GH provided suggestions to improve it. All authors read and
approved the final manuscript.
Funding The authors did not receive support from any organization
for the submitted work.
Declarations
Conflict of interest The authors declare that the research was con-
ducted in the absence of any commercial or financial relationships that
could be construed as a potential conflict of interest.
Informed consent Not applicable.
Ethics approval and consent to participate Not applicable.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
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